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Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled, 2-Part Study of Orally Administered ALS-008176 to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Dosing and Multiple Ascending Dosing in Infants Hospitalized with Respiratory Syncytial Virus (RSV) Infection

Summary
EudraCT number	2013-005104-33
Trial protocol	GB FR RO
Global end of trial date	15 Feb 2018

Results information
Results version number	v2(current)
This version publication date	01 Mar 2019
First version publication date	01 Dec 2018
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

ALS-8176-503

ISRCTN number

US NCT number

NCT02202356

WHO universal trial number (UTN)

Sponsor organisation name

Alios BioPharma

Sponsor organisation address

260 E. Grand Ave, South San Francisco CA, United States, 94080

Public contact

Clinical Registry group, Alios BioPharma, GDeLaRos@its.jnj.com

Scientific contact

Clinical Registry group, Alios BioPharma, GDeLaRos@its.jnj.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-001758-PIP01-15

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

15 Feb 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

15 Feb 2018

Global end of trial reached?

Yes

Global end of trial date

15 Feb 2018

Was the trial ended prematurely?

Main objective of the trial

The main objective of this study was to evaluate the safety and tolerability of single and multiple doses of ALS-008176.

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with good clinical practices and applicable regulatory requirements. Safety was evaluated throughout the study and included adverse events (AEs), vital signs, laboratory assessments (routine hematology, biochemistry, coagulation and urinalysis, 12-lead electrocardiogram (ECG), and physical examination.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Jul 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 2

Country: Number of subjects enrolled

Chile: 12

Country: Number of subjects enrolled

Colombia: 7

Country: Number of subjects enrolled

France: 14

Country: Number of subjects enrolled

United Kingdom: 22

Country: Number of subjects enrolled

Japan: 38

Country: Number of subjects enrolled

New Zealand: 9

Country: Number of subjects enrolled

Panama: 25

Country: Number of subjects enrolled

Thailand: 27

Country: Number of subjects enrolled

Taiwan: 5

Country: Number of subjects enrolled

United States: 20

Worldwide total number of subjects

181

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

180

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 181 subjects were randomized and received ALS-008176 or Placebo.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

SAD: ALS-008176 (1.37 mg/kg)

Arm description

Subjects received single oral dose of 1.37 milligrams per kilogram (mg/kg) of ALS-008176.

Arm type

Experimental

Investigational medicinal product name

ALS-008176

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received single dose of 1.37 mg/kg of ALS-8176 orally.

SAD: ALS-008176 (4.1 mg/kg)

Arm description

Subjects received single oral dose of 4.1 mg/kg of ALS-008176.

Arm type

Experimental

Investigational medicinal product name

ALS-008176

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received single dose of 4.1 mg/kg of ALS-008176 orally.

SAD: ALS-008176 (12 mg/kg)

Arm description

Subjects received single oral dose of 12 mg/kg of ALS-008176.

Arm type

Experimental

Investigational medicinal product name

ALS-008176

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received single dose of 12 mg/kg of ALS-008176 orally.

SAD: ALS-008176 (25 mg/kg)

Arm description

Subjects received single oral dose of 25 mg/kg of ALS-008176.

Arm type

Experimental

Investigational medicinal product name

ALS-008176

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received single dose of 25 mg/kg of ALS-008176 orally.

MAD: ALS-008176 (4.1/1.37 mg/kg)

Arm description

Subjects received 1 loading dose of 4.1 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 1.37 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Arm type

Experimental

Investigational medicinal product name

ALS-008176

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 1 loading dose of 4.1 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 1.37 mg/kg of ALS-008176 twice daily for 5 consecutive days.

MAD: ALS-008176 (10/2 mg/kg)

Arm description

Subjects received loading dose of 10 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 2 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Arm type

Experimental

Investigational medicinal product name

ALS-008176

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received loading dose of 10 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 2 mg/kg of ALS-008176 twice daily for 5 consecutive days.

MAD: ALS-008176 (30/6 mg/kg)

Arm description

Subjects received loading dose of 30 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 9 doses of 6 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Arm type

Experimental

Investigational medicinal product name

ALS-008176

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received loading dose of 30 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 6 mg/kg of ALS-008176 twice daily for 5 consecutive days.

MAD: ALS-008176 (30/10 mg/kg)

Arm description

Subjects received loading dose of 30 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 10 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Arm type

Experimental

Investigational medicinal product name

ALS-008176

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received loading dose of 30 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 10 mg/kg of ALS-008176 twice daily for 5 consecutive days.

MAD: ALS-008176 (40/20 mg/kg)

Arm description

Subjects received loading dose of 40 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 20 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Arm type

Experimental

Investigational medicinal product name

ALS-008176

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received loading dose of 40 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 20 mg/kg of ALS-008176 twice daily for 5 consecutive days.

MAD: ALS-008176 (60/40 mg/kg)

Arm description

Subjects received loading dose of 60 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 40 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Arm type

Experimental

Investigational medicinal product name

ALS-008176

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received loading dose of 60 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 40 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Placebo

Arm description

Subjects received Placebo orally in SAD and MAD part.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received Placebo orally in SAD and MAD part.

Number of subjects in period 1	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	Placebo
Started	18	18	14	3	5	14	8	17	18	16	50
Completed	18	17	14	2	5	14	8	17	15	16	47
Not completed	0	1	0	1	0	0	0	0	3	0	3
Adverse Event (Serious-Non Fatal)	-	-	-	-	-	-	-	-	1	-	-
Lost to follow-up	-	1	-	-	-	-	-	-	-	-	1
Withdrawal by subject	-	-	-	1	-	-	-	-	2	-	2

Baseline characteristics

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Reporting group title

SAD: ALS-008176 (1.37 mg/kg)

Reporting group description

Subjects received single oral dose of 1.37 milligrams per kilogram (mg/kg) of ALS-008176.

Reporting group title

SAD: ALS-008176 (4.1 mg/kg)

Reporting group description

Subjects received single oral dose of 4.1 mg/kg of ALS-008176.

Reporting group title

SAD: ALS-008176 (12 mg/kg)

Reporting group description

Subjects received single oral dose of 12 mg/kg of ALS-008176.

Reporting group title

SAD: ALS-008176 (25 mg/kg)

Reporting group description

Subjects received single oral dose of 25 mg/kg of ALS-008176.

Reporting group title

MAD: ALS-008176 (4.1/1.37 mg/kg)

Reporting group description

Subjects received 1 loading dose of 4.1 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 1.37 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

MAD: ALS-008176 (10/2 mg/kg)

Reporting group description

Subjects received loading dose of 10 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 2 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

MAD: ALS-008176 (30/6 mg/kg)

Reporting group description

Subjects received loading dose of 30 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 9 doses of 6 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

MAD: ALS-008176 (30/10 mg/kg)

Reporting group description

Subjects received loading dose of 30 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 10 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

MAD: ALS-008176 (40/20 mg/kg)

Reporting group description

Subjects received loading dose of 40 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 20 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

MAD: ALS-008176 (60/40 mg/kg)

Reporting group description

Subjects received loading dose of 60 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 40 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

Placebo

Reporting group description

Subjects received Placebo orally in SAD and MAD part.

Reporting group values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	Placebo	Total
Number of subjects	18	18	14	3	5	14	8	17	18	16	50	181
Title for AgeCategorical
Units: subjects
Newborns (0-28 days)	0	0	0	0	0	1	0	0	0	0	0	1
Infants and toddlers (>28 days-12 months)	18	18	14	3	5	13	8	17	18	16	50	180
Title for AgeContinuous
Units: months
arithmetic mean (standard deviation)	4 ± 2.8	4.2 ± 2.66	5.7 ± 2.77	5 ± 2.29	5 ± 3.32	3.2 ± 2.89	2.3 ± 1.39	3.5 ± 2.62	4.2 ± 2.94	4.2 ± 3.39	4.1 ± 3.23	-
Title for Gender
Units: subjects
Female	9	8	3	1	3	4	3	6	4	6	23	70
Male	9	10	11	2	2	10	5	11	14	10	27	111

End points

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Reporting group title

SAD: ALS-008176 (1.37 mg/kg)

Reporting group description

Subjects received single oral dose of 1.37 milligrams per kilogram (mg/kg) of ALS-008176.

Reporting group title

SAD: ALS-008176 (4.1 mg/kg)

Reporting group description

Subjects received single oral dose of 4.1 mg/kg of ALS-008176.

Reporting group title

SAD: ALS-008176 (12 mg/kg)

Reporting group description

Subjects received single oral dose of 12 mg/kg of ALS-008176.

Reporting group title

SAD: ALS-008176 (25 mg/kg)

Reporting group description

Subjects received single oral dose of 25 mg/kg of ALS-008176.

Reporting group title

MAD: ALS-008176 (4.1/1.37 mg/kg)

Reporting group description

Subjects received 1 loading dose of 4.1 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 1.37 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

MAD: ALS-008176 (10/2 mg/kg)

Reporting group description

Subjects received loading dose of 10 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 2 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

MAD: ALS-008176 (30/6 mg/kg)

Reporting group description

Subjects received loading dose of 30 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 9 doses of 6 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

MAD: ALS-008176 (30/10 mg/kg)

Reporting group description

Subjects received loading dose of 30 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 10 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

MAD: ALS-008176 (40/20 mg/kg)

Reporting group description

Subjects received loading dose of 40 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 20 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

MAD: ALS-008176 (60/40 mg/kg)

Reporting group description

Subjects received loading dose of 60 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 40 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

Placebo

Reporting group description

Subjects received Placebo orally in SAD and MAD part.

Subject analysis set title

SAD: Placebo

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received Placebo orally in SAD part.

Subject analysis set title

MAD: Placebo

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received Placebo orally in MAD part.

Primary: SAD: Number of Subjects with Treatment Emergent Adverse Events (TEAEs)

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End point title

SAD: Number of Subjects with Treatment Emergent Adverse Events (TEAEs) ^[1] ^[2]

End point description

An adverse event is any untoward medical event that occurs in a subjects administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Safety Analysis Set defined as all randomized subjects who received at least 1 dose of study medication.

End point type

Primary

End point timeframe

Approximately 4 years

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	SAD: Placebo	MAD: Placebo
Number of subjects analysed	18	18	14	3	5	14	8	17	18	16	17	33
Units: Subjects	14	8	6	2	4	9	4	13	13	14	4	20

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Physical Examination (Temperature)

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End point title

SAD: Change From Baseline in Physical Examination (Temperature) ^[3] ^[4]

End point description

Change from baseline in temperature was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

Baseline up to Day 7

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Degree celsius
arithmetic mean (standard deviation)
Change at Day 1, 0.5-1h (n=18,18,14,3,15)	-0.1 ± 0.80	-0.2 ± 0.56	-0.3 ± 0.78	0.3 ± 1.74	-0.0 ± 0.74
Change at Day 2, 24h (n=18, 18, 14, 3, 17)	-0.0 ± 0.68	-0.1 ± 0.64	-0.5 ± 0.77	-0.3 ± 1.07	-0.1 ± 0.66
Change at Day 3 (n=15, 14, 11, 2, 8)	-0.1 ± 0.59	0.0 ± 0.66	-0.7 ± 0.76	-1.3 ± 1.48	-0.0 ± 0.57
Change at Day 4 (n=12, 6, 7, 1, 3)	-0.2 ± 0.64	0.0 ± 0.58	-0.6 ± 0.79	0.7 ± 99999	-0.5 ± 0.35
Change at Day 5 (n=6, 4, 6, 0, 2)	0.1 ± 0.57	-0.0 ± 0.45	-0.8 ± 0.71	99999 ± 99999	-0.4 ± 0.21
Change at Day 6 (n=1, 2, 2, 0, 5, 1)	0.2 ± 99999	0.1 ± 0.28	-0.4 ± 0.99	99999 ± 99999	-1.7 ± 99999
Change at Day 7 (n=18, 17, 14, 2, 16)	-0.1 ± 0.74	-0.1 ± 0.63	-0.9 ± 0.87	-1.2 ± 0.78	-0.2 ± 0.68

No statistical analyses for this end point

Primary: SAD: Change From Baseline for Physical Examination (Respiratory Rate)

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End point title

SAD: Change From Baseline for Physical Examination (Respiratory Rate) ^[5] ^[6]

End point description

Change from baseline in respiratory rate was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

Baseline up to Day 7

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Breaths per minute
arithmetic mean (standard deviation)
Change at Day 1, (n=18,18,14,3,16)	1.7 ± 12.53	1.8 ± 6.53	-0.1 ± 5.88	-1.3 ± 4.16	0.8 ± 12.31
Change at Day 2, (n=18, 18, 14, 3, 17)	-2.2 ± 13.17	-2.4 ± 6.20	-2.4 ± 8.49	2.7 ± 1.53	-2.6 ± 12.56
Change at Day 3 (n=15, 14, 10, 2, 8)	-2.3 ± 11.63	-3.1 ± 8.34	-7.6 ± 6.83	3.0 ± 1.41	-0.8 ± 16.99
Change at Day 4 (n=11, 6, 6, 1, 3)	-1.2 ± 16.77	-3.3 ± 8.66	-4.7 ± 7.76	0.0 ± 99999	2.7 ± 12.70
Change at Day 5 (n=5, 4, 5, 0, 2)	-4.6 ± 14.62	-4.0 ± 8.04	-5.2 ± 6.10	99999 ± 99999	2.0 ± 2.83
Change at Day 6 (n=1, 2, 2, 0, 1)	-10.0 ± 99999	-6.0 ± 5.66	2.0 ± 8.49	99999 ± 99999	0.0 ± 99999
Change at Day 7 (n=18, 17, 14, 2, 16)	-9.2 ± 12.50	-3.0 ± 9.05	-5.3 ± 6.76	1.0 ± 1.41	-5.0 ± 12.77

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Physical Examination (Heart Rate)

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End point title

SAD: Change From Baseline in Physical Examination (Heart Rate) ^[7] ^[8]

End point description

Change from baseline in Heart rate was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

Baseline up to Day 7

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Beats per minute
arithmetic mean (standard deviation)
Change at Day 1, 0.5-1h (n=18,18,14,3,16)	-4.8 ± 21.66	-3.1 ± 25.99	-12.7 ± 20.37	-6.3 ± 19.09	-10.9 ± 20.58
Change at Day 2, 24h (n=18,18,14,3,17)	-10.5 ± 26.83	-3.9 ± 18.46	-13.5 ± 29.85	6.7 ± 23.18	-13.9 ± 22.80
Change at Day 3 (n=15, 14, 11, 2, 8)	-5.0 ± 30.03	-6.8 ± 22.95	-11.6 ± 23.35	10.0 ± 32.53	-11.3 ± 18.84
Change at Day 4 (n=12, 6, 7, 1, 3)	-12.3 ± 26.70	-6.8 ± 32.18	-12.1 ± 19.68	4.0 ± 99999	1.3 ± 2.31
Change at Day 5 (n=6, 4, 6, 0, 2)	-12.7 ± 23.73	-0.3 ± 28.23	-21.0 ± 19.46	99999 ± 99999	0.0 ± 8.49
Change at Day 6 (n=1, 2, 2, 0, 1)	5.0 ± 99999	-11.5 ± 48.79	4.0 ± 29.70	99999 ± 99999	-48.0 ± 99999
Change at Day 7 (n=18, 17, 14, 2, 16)	-17.2 ± 25.76	-6.1 ± 26.30	-10.7 ± 28.48	8.0 ± 1.41	-14.4 ± 18.86

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Physical Examination (Weight)

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End point title

SAD: Change From Baseline in Physical Examination (Weight) ^[9] ^[10]

End point description

Change from Baseline in weight was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "n" indicates number of subjects evaluated at specified timepoints.

End point type

Primary

End point timeframe

Baseline, Day 2 and Day 7

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Kilogram (kg)
arithmetic mean (standard deviation)
Change at Day 2, 24h (n=18,17,13,3,12)	-0.0 ± 0.37	-0.0 ± 0.08	0.0 ± 0.21	0.0 ± 0.22	-0.0 ± 0.10
Change at Day 7 (n=18, 17, 14, 2, 16)	-0.1 ± 0.45	-0.2 ± 0.45	-0.1 ± 0.14	0.2 ± 0.30	-0.1 ± 0.27

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Physical Examination (Body Mass Index [BMI])

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End point title

SAD: Change From Baseline in Physical Examination (Body Mass Index [BMI]) ^[11] ^[12]

End point description

Change from baseline in BMI was assessed and measured in kilogram per square meter (kg/m^2). Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "n" indicates number of subjects evaluated at specified timepoints.

End point type

Primary

End point timeframe

Baseline, Day 2 and Day 7

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: kg/m^2
arithmetic mean (standard deviation)
Change at Day 2, 24h (n=17, 16, 13, 3, 12)	-0.2 ± 1.09	-0.0 ± 0.24	-0.0 ± 0.51	0.1 ± 0.61	-0.1 ± 0.25
Change at Day 7 (n=17, 16, 14, 2, 16)	-0.2 ± 1.25	-0.5 ± 1.06	-0.2 ± 0.35	0.4 ± 0.65	-0.1 ± 0.63

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Physical Examination (Blood Pressure: Systolic Blood Pressure [sBP] and Distolic Blood Pressure [dBP])

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End point title

SAD: Change From Baseline in Physical Examination (Blood Pressure: Systolic Blood Pressure [sBP] and Distolic Blood Pressure [dBP]) ^[13] ^[14]

End point description

Change from baseline in Blood pressure: sBP and dBP was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

Baseline up to Day 7

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Millimeter of Mercury (mmHg)
arithmetic mean (standard deviation)
sBP:Change at Day 1, (n=17,18,12,3,14)	-2.5 ± 9.99	-0.6 ± 9.22	5.4 ± 23.05	1.0 ± 9.64	5.6 ± 12.84
sBP:Change at Day 2, (n=17,18,13,3,13)	-5.4 ± 18.46	-0.9 ± 8.16	4.5 ± 18.21	7.0 ± 7.94	3.8 ± 17.82
sBP:Change at Day 3 (n=14, 13, 10, 1, 7)	-5.1 ± 12.25	1.5 ± 8.84	0.0 ± 11.99	-3.0 ± 99999	5.9 ± 5.15
sBP:Change at Day 4 (n=9, 6, 6, 0, 3)	-5.3 ± 14.10	1.8 ± 16.73	-0.2 ± 12.06	99999 ± 99999	11.3 ± 14.47
sBP:Change at Day 5 (n=4, 4, 5, 0, 2)	-0.3 ± 3.69	-9.5 ± 13.33	3.2 ± 14.75	99999 ± 99999	5.0 ± 12.73
sBP:Change at Day 6 (n=1, 1, 2, 0, 1)	-5.0 ± 99999	5.0 ± 99999	-7.5 ± 0.71	99999 ± 99999	4.0 ± 99999
sBP:Change at Day 7 (n=16, 16, 12, 2, 14)	-9.8 ± 14.80	2.6 ± 21.07	4.9 ± 31.61	1.0 ± 12.73	7.1 ± 13.95
dBP:Change at Day 1 (n=17, 18, 12, 3, 14)	-3.4 ± 10.95	5.1 ± 16.46	3.7 ± 14.57	1.0 ± 17.35	0.5 ± 15.30
dBP:Change at Day 2 (n=17, 18, 13, 3, 13)	-5.2 ± 12.20	3.3 ± 11.65	1.6 ± 16.19	-1.3 ± 14.98	5.0 ± 14.66
dBP:Change at Day 3 (n=14, 13, 10, 1, 7)	-5.6 ± 10.02	4.3 ± 14.29	1.2 ± 8.23	-11.0 ± 99999	-5.3 ± 8.94
dBP:Change at Day 4 (n=9, 6, 6, 0, 3)	-4.3 ± 6.65	-0.3 ± 10.91	-10.8 ± 12.81	99999 ± 99999	-5.0 ± 17.78
dBP:Change at Day 5 (n=4, 4, 5, 0, 2)	2.5 ± 6.45	-2.8 ± 9.91	-3.6 ± 9.07	99999 ± 99999	-16.0 ± 5.66
dBP:Change at Day 6 (n=1, 1, 2, 0, 1)	15.0 ± 99999	0.0 ± 99999	-3.5 ± 6.36	99999 ± 99999	1.0 ± 99999
dBP:Change at Day 7 (n=16, 16, 12, 2, 14)	-3.7 ± 12.99	2.1 ± 15.82	-1.3 ± 14.28	15.5 ± 0.71	6.4 ± 13.21

No statistical analyses for this end point

Primary: SAD: Change From Baseline for 12-lead Electrocardiogram (ECG) Parameters

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End point title

SAD: Change From Baseline for 12-lead Electrocardiogram (ECG) Parameters ^[15] ^[16]

End point description

Change from Baseline in ECG (RR interval, PR interval, QRS interval, QT interval, QTcB interval, QTcF interval) was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "n" indicates number of subjects evaluated at specified timepoints.

End point type

Primary

End point timeframe

Baseline up to Day 7

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: millisecond (msec)
arithmetic mean (standard deviation)
RR interval: Change at Day 1(n=18, 16, 14, 3, 17)	5.7 ± 79.52	26.6 ± 82.92	38.0 ± 92.81	5.3 ± 104.58	11.6 ± 54.87
RR interval: Change at Day 7(n=18, 16, 13, 2, 16)	10.7 ± 72.99	2.7 ± 60.06	36.5 ± 107.57	61.5 ± 21.92	38.6 ± 73.31
PR interval: Change at Day 1(n=18, 16, 14, 3, 17)	0.3 ± 22.78	0.4 ± 18.74	-2.7 ± 15.48	2.7 ± 7.02	-2.4 ± 15.26
PR interval: Change at Day 7(n=18, 16, 13, 2, 16)	-6.2 ± 21.59	-4.8 ± 21.86	-5.9 ± 11.81	-6.0 ± 16.97	3.2 ± 13.18
QRS interval:Change at Day 1(n=18, 16, 14, 3, 17)	-0.6 ± 24.77	-1.6 ± 11.75	-5.7 ± 11.66	-1.0 ± 2.65	-0.4 ± 19.13
QRS interval:Change at Day 7(n=18, 16, 13, 2, 16)	-4.3 ± 21.27	1.8 ± 16.47	-3.8 ± 12.43	2.0 ± 5.66	-1.1 ± 17.37
QT interval:Change at Day 1(n= 18, 16, 14, 3, 17)	0.9 ± 44.51	1.8 ± 23.10	-7.6 ± 66.76	4.0 ± 30.27	-3.5 ± 43.52
QT interval:Change at Day 7(n=18, 16, 13, 2, 16)	3.7 ± 49.72	0.7 ± 26.66	-3.5 ± 64.44	43.5 ± 24.75	4.5 ± 38.97
QTcB interval:Change at Day 1(n=18,16,13,3,17)	-2.7 ± 65.31	-9.2 ± 21.47	-13.1 ± 44.88	3.0 ± 5.29	-20.7 ± 72.59
QTcB interval:Change at Day 7(n=18, 16,13,2,16)	-3.3 ± 68.45	4.6 ± 40.58	-2.4 ± 36.56	36.5 ± 23.33	-17.8 ± 68.46
QTcF interval:Change at Day 1(n=18, 16,14,3,17)	-0.4 ± 55.72	-3.2 ± 16.70	-4.6 ± 40.59	3.3 ± 10.69	-12.9 ± 82.87
QTcF interval:Change at Day 7(n=18,16,13,2,16)	1.3 ± 60.19	5.1 ± 30.78	1.9 ± 28.37	40.5 ± 24.75	-5.3 ± 52.04

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Alkaline Phosphatase [AP], Alanine Aminotransferase [ALA], Aspartate Aminotransferase [ASA], Creatine Kinase [CrK])

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End point title

SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Alkaline Phosphatase [AP], Alanine Aminotransferase [ALA], Aspartate Aminotransferase [ASA], Creatine Kinase [CrK]) ^[17] ^[18]

End point description

Change from baseline in Serum Chemistry-AP, ALA, ASA, CrK were assessed. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline, Day 1 and Day 7

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Microkatal per liter
arithmetic mean (standard deviation)
AP:Change at Day 1, 3h (n=7, 7, 6, 1, 8)	-0.300 ± 0.4948	-0.440 ± 1.3063	-0.094 ± 0.1361	-0.167 ± 99999	0.050 ± 0.2049
AP:Change at Day 1, 7h (n=7, 8, 7, 2 ,6)	-0.241 ± 0.2095	-0.204 ± 0.5564	-0.088 ± 0.4043	0.208 ± 0.1061	-0.119 ± 0.3383
AP:Change at Day 7 (n=18, 16, 13, 2, 16)	0.172 ± 0.9051	0.414 ± 0.8600	0.012 ± 0.7169	1.125 ± 0.2004	0.362 ± 1.1151
ALA:Change at Day 1, 3h (n=7, 7, 7, 1, 7)	-0.009 ± 0.0841	-0.008 ± 0.0337	-0.012 ± 0.0826	-0.017 ± 99999	0.000 ± 0.0491
ALA:Change at Day 1, 7h (n=7, 8, 7, 2, 6)	-0.062 ± 0.0967	0.060 ± 0.2745	-0.002 ± 0.0619	0.000 ± 0.0000	-0.025 ± 0.0673
ALA:Change at Day 7 (n=18, 17, 13, 2, 16)	0.040 ± 0.2101	-0.376 ± 1.2695	0.077 ± 0.3084	0.000 ± 0.0707	0.020 ± 0.1564
ASA:Change at Day 1, 3h (n=6, 7, 5, 0, 6)	-0.041 ± 0.0886	0.022 ± 0.1012	0.103 ± 0.1639	99999 ± 99999	0.083 ± 0.0803
ASA:Change at Day 1, 7h (n=5, 6, 6, 2, 5)	-0.004 ± 0.0766	0.217 ± 0.4365	-0.061 ± 0.1754	0.092 ± 0.1061	0.200 ± 0.3156
ASA:Change at Day 7 (n=15, 14, 12, 2, 12)	0.027 ± 0.2693	-0.252 ± 0.7332	0.032 ± 0.2700	0.083 ± 0.0943	-0.050 ± 0.2278
CrK:Change at Day 1, 3h (n=7, 6, 6, 1, 8)	-0.100 ± 1.3554	-0.967 ± 2.1592	0.008 ± 0.4103	0.033 ± 99999	-0.517 ± 0.8730
CrK:Change at Day 1, 7h (n=6, 7, 7, 2, 4)	-0.172 ± 0.4526	-0.040 ± 0.6998	-0.031 ± 0.4879	0.108 ± 0.0589	-0.146 ± 0.7974
CrK:Change at Day 7 (n=17, 13, 13, 2, 13)	0.001 ± 1.9922	-1.500 ± 4.0774	2.958 ± 9.4720	0.675 ± 0.1532	-0.044 ± 1.9820

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Bilirubin, Direct Bilirubin [DB], and Indirect Bilirubin [IB], Creatinine [Cr])

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End point title

SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Bilirubin, Direct Bilirubin [DB], and Indirect Bilirubin [IB], Creatinine [Cr]) ^[19] ^[20]

End point description

Change From Baseline in Serum Chemistry-Bilirubin, Direct Bilirubin (DB), Indirect Bilirubin (IB), and Creatinine (Cr) were assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

For DB and IB: From Baseline, Day 1, Day 3 and Day 7 and for Cr: From Baseline, Day 1, Day 3, Day 4 and Day 7

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Micromoles per liter (mcmol/L)
arithmetic mean (standard deviation)
Bilirubin:Change at Day 1, 3h (n=7,6,7,1,8)	-2.178 ± 3.2316	-0.599 ± 0.9288	-0.942 ± 1.3241	0.000 ± 99999	-0.516 ± 1.8990
Bilirubin:Change at Day 1, 7h (n=7,7,7,2,6)	-0.310 ± 0.4754	-0.216 ± 2.1765	-0.126 ± 1.5381	-1.000 ± 1.4142	-2.594 ± 4.7885
Bilirubin:Change at Day 3 (n=1, 0, 0, 0, 0)	0.171 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Bilirubin: Change at Day 7 (n=18, 15, 13, 2, 16)	-1.809 ± 5.7567	0.390 ± 3.7937	0.155 ± 2.7809	-0.500 ± 0.7071	-0.142 ± 4.7240
DB: Change at Day 1, 3h (n=5, 5, 4, 0, 6)	-1.626 ± 1.0669	-0.039 ± 0.7201	-0.385 ± 0.8872	99999 ± 99999	-0.366 ± 0.8641
DB: Change at Day 1, 7h (n=4, 5, 5, 1, 3)	0.428 ± 0.8550	0.000 ± 1.0747	0.239 ± 0.2294	0.000 ± 99999	-0.570 ± 0.9873
DB: Change at Day 3 (n=1, 0, 0, 0, 0)	0.171 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
DB: Change at Day 7 (n=10, 10, 9, 1, 9)	0.117 ± 0.8729	0.425 ± 1.7729	-0.247 ± 1.3895	0.000 ± 99999	1.374 ± 4.2736
IB: Change at Day 1, 3h (n=3, 3, 1, 0, 4)	-1.430 ± 4.0490	-0.570 ± 0.9873	-0.342 ± 99999	99999 ± 99999	-0.770 ± 1.2527
IB: Change at Day 1, 7h (n=3, 1, 3, 1, 2)	-0.627 ± 0.9418	-1.710 ± 99999	0.342 ± 2.2361	0.000 ± 99999	-0.941 ± 1.0882
IB: Change as Day 3 (n=1, 0, 0, 0, 0)	0.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
IB: Change at Day 7 (n=7, 4, 4, 1, 6)	0.081 ± 1.6524	-2.693 ± 3.7681	2.309 ± 3.2848	0.000 ± 99999	1.254 ± 3.1728
Cr: Change at Day 1, 3h (n=6, 7, 7, 1, 8)	-0.167 ± 1.6021	-1.449 ± 3.8813	-0.027 ± 4.2436	0.000 ± 99999	3.774 ± 9.3274
Cr: Change at Day 1, 7h (n=7, 8, 7, 2, 7)	-0.538 ± 5.8116	-1.013 ± 3.8128	-0.126 ± 7.1625	-0.500 ± 0.7071	-2.389 ± 3.8129
Cr: Change at Day 3 (n=1, 0, 1, 0, 0)	-0.884 ± 99999	99999 ± 99999	0.000 ± 99999	99999 ± 99999	99999 ± 99999
Cr: Change at Day 4 (n=0, 1, 0, 0, 0)	99999 ± 99999	-6.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cr: Change at Day 7 (n=18, 17, 13, 2, 16)	1.403 ± 2.3512	2.024 ± 3.6523	3.386 ± 11.6813	1.500 ± 2.1213	0.353 ± 6.7510

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Blood Urea Nitrogen [BUN], Derived Urea [DU], Chloride [Cl], Bicarbonate [BiC], Glucose [Glu], Potassium [K], Sodium[Na])

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End point title

SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Blood Urea Nitrogen [BUN], Derived Urea [DU], Chloride [Cl], Bicarbonate [BiC], Glucose [Glu], Potassium [K], Sodium[Na]) ^[21] ^[22]

End point description

Change from baseline for clinical laboratory parameter (Serum chemistry- Blood Urea Nitrogen [BUN], Derived Urea [DU], Chloride [Cl], Bicarbonate [BiC], Glucose [Glu], Potassium [K], and Sodium [Na]) was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

For BUN and DU: From Baseline, Day 1, Day 3, Day 7; for Cl, K and Na: From baseline, Day 1, 3, 4, 6 and Day 7

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
BUN: Change at Day 1, 3h Postdose(n=6, 6, 4, 0, 4)	0.075 ± 0.3764	0.292 ± 0.6872	-0.018 ± 0.5136	99999 ± 99999	0.062 ± 0.3969
BUN: Change at Day 1, 7h Postdose(n=4, 6, 5, 0, 4)	0.134 ± 0.5518	-0.014 ± 0.7761	-0.221 ± 0.5544	99999 ± 99999	-0.687 ± 0.5884
BUN: Change at Day 3 (n=0, 0, 1, 0, 0)	99999 ± 99999	99999 ± 99999	0.678 ± 99999	99999 ± 99999	99999 ± 99999
BUN: Change at Day 7 (n=10, 11, 9, 1, 8)	0.597 ± 0.7556	0.831 ± 1.0460	0.409 ± 0.7407	1.071 ± 99999	0.228 ± 1.4166
DU: Change at Day 1, 3h(n=6, 8, 7, 1, 8)	-0.261 ± 0.5504	0.151 ± 0.6290	-0.339 ± 0.6782	0.000 ± 99999	-0.106 ± 0.3757
DU: Change at Day 1, 7h(n=7, 8, 7, 1, 7)	-0.038 ± 0.5881	0.080 ± 0.6776	-0.015 ± 0.6182	0.200 ± 99999	-0.393 ± 0.9118
DU: Change at Day 3 (n=0, 0, 1, 0, 0)	99999 ± 99999	99999 ± 99999	0.678 ± 99999	99999 ± 99999	99999 ± 99999
DU: Change at Day 7 (n=17, 17, 13, 2, 15)	0.217 ± 0.6580	0.926 ± 1.0024	0.652 ± 0.9884	0.836 ± 0.3330	0.368 ± 1.1038
Cl: Change at Day 1, 3h Postdose (n=6, 8, 6, 0 7)	-1.167 ± 2.1370	-1.625 ± 2.0659	0.400 ± 2.9933	99999 ± 99999	-0.643 ± 1.9730
Cl: Change at Day 1; 7h Postdose(n=7, 8, 6, 2, 5)	-0.286 ± 1.7995	-0.575 ± 2.3457	-0.500 ± 3.1464	0.000 ± 0.0000	-0.560 ± 2.9846
Cl: Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	-6.300 ± 99999	99999 ± 99999	99999 ± 99999	-3.800 ± 99999
Cl: Change at Day 4 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-1.100 ± 99999
Cl: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-4.300 ± 99999
Cl: Change at Day 7 (n=17, 16, 13, 2, 13)	0.176 ± 3.5397	-0.131 ± 3.3380	0.015 ± 2.9274	3.000 ± 0.0000	0.469 ± 2.8238
BiC:Change at Day 1, 3h Postdose (n=6, 7, 6, 0, 7)	0.367 ± 1.7500	1.771 ± 2.8929	0.667 ± 2.4312	99999 ± 99999	-2.686 ± 4.7355
BiC:Change at Day 1; 7h Postdose (n=7, 8, 7, 2, 5)	-0.614 ± 2.6143	0.325 ± 2.1881	0.157 ± 2.3999	-0.050 ± 0.3536	-1.440 ± 2.7181
BiC: Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	-1.100 ± 99999	99999 ± 99999	1.600 ± 99999
BiC: Change at Day 4 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-2.500 ± 99999
BiC: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	2.200 ± 99999
BiC: Change at Day 7 (n=16, 14, 13, 2, 11)	-2.463 ± 4.5964	-2.486 ± 2.5792	-1.015 ± 3.2761	-3.200 ± 0.0000	-2.073 ± 3.5508
Glu: Change at Day 1, 3h(n=6, 6, 6, 0, 7)	-0.559 ± 1.0626	-1.638 ± 3.1932	0.348 ± 0.5935	99999 ± 99999	0.144 ± 0.6468
Glu: Change at Day 1, 7h(n=7, 8, 6, 2, 5)	-0.370 ± 0.7408	-0.468 ± 1.0589	6.510 ± 13.7761	-0.244 ± 0.2040	-0.418 ± 0.9007
Glu: Change at Day 7 (n=16, 17, 12, 2, 14)	-0.973 ± 1.1516	-1.020 ± 1.8882	-0.455 ± 0.6583	-1.239 ± 0.6526	-0.636 ± 1.2004
K: Change at Day 1, 3h Postdose(n=7, 8, 7, 1, 8)	-0.029 ± 0.3450	-0.083 ± 0.6207	-0.069 ± 0.3458	0.800 ± 99999	0.200 ± 0.5555
K: Change at Day 1, 7h Postdose(n=7, 8, 6, 2, 6)	-0.416 ± 0.4176	-0.063 ± 0.5208	-0.143 ± 0.6191	0.750 ± 0.7778	0.592 ± 1.0754
K: Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	0.480 ± 99999	99999 ± 99999	0.350 ± 99999
K: Change at Day 4 (n=0, 1, 0, 0, 1)	99999 ± 99999	0.300 ± 99999	99999 ± 99999	99999 ± 99999	0.620 ± 99999
K: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.840 ± 99999
K: Change at Day 7 (n=18, 17, 13, 2, 16)	0.281 ± 0.7417	0.324 ± 0.8241	0.437 ± 1.2304	0.400 ± 0.2828	0.312 ± 0.7808
Na: Change at Day 1, 3h(n=7, 8, 7, 1, 8)	-1.143 ± 0.9163	-0.988 ± 2.9406	1.143 ± 3.5322	0.000 ± 99999	-1.000 ± 3.0706
Na: Change at Day 1, 7h(n=7, 8, 6, 2, 7)	-0.543 ± 2.9563	-0.500 ± 2.7255	-1.833 ± 4.8339	0.000 ± 0.0000	0.000 ± 2.8868
Na: Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	-1.000 ± 99999	99999 ± 99999	-1.000 ± 99999
Na: Change at Day 4 (n=0, 1, 0, 0, 1)	99999 ± 99999	3.000 ± 99999	99999 ± 99999	99999 ± 99999	-2.000 ± 99999
Na: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-3.000 ± 99999
Na: Change at Day 7 (n=18, 17, 13, 2, 16)	-0.761 ± 2.2968	-0.818 ± 2.9394	0.154 ± 2.8532	0.500 ± 0.7071	-0.063 ± 2.5682

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Clinical laboratory Parameter (Hematology-Reticulocyte Absolute [RA], Platelets [Pl], Leukocytes [LU], Monocytes [MO], Neutrophils [NE])

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End point title

SAD: Change From Baseline in Clinical laboratory Parameter (Hematology-Reticulocyte Absolute [RA], Platelets [Pl], Leukocytes [LU], Monocytes [MO], Neutrophils [NE]) ^[23] ^[24]

End point description

Change from baseline in Hematology- reticulocyte, Absolute (RA), Platelets (Pl), Leukocytes (LU), Monocytes (MO) and Neutrophils (NE) were assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

For RA, MO, NE: From Baseline, Day 1 and Day 7; For Pl, LU: From Baseline, Day 1, Day 3, Day 6 and Day 7

Notes
[23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: 10^9 per liter
arithmetic mean (standard deviation)
RA: Change at Day, 3h (n=1, 1, 2, 1, 2)	-3.200 ± 99999	-0.200 ± 99999	-2.250 ± 2.4749	-0.200 ± 99999	3.750 ± 0.4950
RA: Change at Day 1, 7h (n=3, 3, 1, 1, 1)	3.333 ± 6.1101	2.873 ± 5.2253	33.000 ± 99999	5.300 ± 99999	38.640 ± 99999
RA: Change at Day 7 (n=5, 5, 3, 0, 6)	18.920 ± 14.0901	45.500 ± 28.2952	83.533 ± 28.3285	99999 ± 99999	48.710 ± 32.0216
Pl: Change at Day 1, 3h (n=7, 8, 7, 1, 7)	15.429 ± 51.6135	-11.500 ± 104.8768	17.143 ± 83.8718	52.000 ± 99999	28.000 ± 57.2655
Pl: Change at Day 1, 7h (n=7, 8, 6, 2, 5)	4.286 ± 58.9992	81.375 ± 147.4807	-13.667 ± 73.7500	17.500 ± 10.6066	-21.400 ± 246.0616
Pl: Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	77.000 ± 99999	99999 ± 99999	-95.000 ± 99999
Pl: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	45.000 ± 99999
Pl: Change at Day 7 (n=17, 16, 12, 0, 16)	239.765 ± 250.8260	214.438 ± 204.2335	226.750 ± 181.5404	99999 ± 99999	188.375 ± 144.8916
LU: Change at Day 1, 3h (n=7, 8, 7, 1, 7)	-1.194 ± 3.1878	-2.008 ± 2.9722	1.864 ± 6.7045	1.470 ± 99999	0.254 ± 2.0285
LU: Change at Day 1, 7h (n=7, 8, 6, 2, 6)	-1.730 ± 3.6807	1.366 ± 2.3019	1.073 ± 2.3062	0.210 ± 0.1273	-0.523 ± 6.4347
LU: Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	5.500 ± 99999	99999 ± 99999	-12.900 ± 99999
LU: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-6.800 ± 99999
LU: Change at Day 7 (n=17, 16, 12, 0, 16)	0.549 ± 3.5909	2.682 ± 4.6478	3.398 ± 4.6757	99999 ± 99999	0.431 ± 4.6811
MO: Change at Day 1, 3h (n=4, 7, 5, 1, 7)	-0.4108 ± 0.34710	-0.5242 ± 1.18012	-0.0629 ± 0.75397	0.4300 ± 99999	-0.0325 ± 0.36931
MO: Change at Day 1, 7h (n=5, 5, 4, 1, 5)	-0.2473 ± 0.74147	0.2852 ± 0.66781	-0.1637 ± 0.14324	0.0300 ± 99999	0.1278 ± 0.52287
MO: Change at Day 7 (n=12, 12, 8, 0, 15)	-0.5250 ± 1.00177	-0.0051 ± 0.97576	-0.0045 ± 0.75931	99999 ± 99999	-0.0492 ± 0.48357
NE: Change at Day 1, 3h (n=4, 7, 5, 1, 7)	-1.0579 ± 1.81701	-1.0449 ± 1.77922	0.3576 ± 4.94630	-0.7800 ± 99999	-0.2936 ± 1.39078
NE: Change at Day 1, 7h (n=5, 6, 4, 2, 5)	-1.3340 ± 1.49913	1.0500 ± 0.83268	0.6315 ± 1.01518	-1.1300 ± 0.38184	-0.3760 ± 1.51896
NE: Change at Day 7 (n=12, 13, 8, 0, 15)	-1.3650 ± 3.59894	0.8115 ± 2.57739	0.3376 ± 3.02596	99999 ± 99999	0.0527 ± 2.17787

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Reticulocyte Percent, Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, and Lymphocytes/Leukocytes

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End point title

SAD: Change From Baseline in Reticulocyte Percent, Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, and Lymphocytes/Leukocytes ^[25] ^[26]

End point description

Change from baseline in hematology- Reticulocyte Percent (RE), Hematocrit (HeT), Basophils/Leukocytes (B/LU), Eosinophils/Leukocytes (E/LU), Monocytes/Leukocytes (MO/LU), Neutrophils/Leukocytes (N/LU), and Lymphocytes/Leukocytes (Ly/LU) were assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint in respective arm. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

For RE: From Baseline to Day 1 and Day 7; For HeT, B/LU, E/LU, Ly/LU, MO/LU and N/LU: From Baseline to Day 1, 3, 6 and Day 7

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Fraction of 1
arithmetic mean (standard deviation)
RE: Change at Day 1 3h (n=5, 7, 4, 0, 4)	0.00138 ± 0.002318	0.00157 ± 0.012323	-0.00143 ± 0.000960	99999 ± 99999	0.00158 ± 0.003021
RE: Change at Day 1, 7h (n=4, 4, 5, 1, 2)	0.00505 ± 0.013516	0.00212 ± 0.003115	-0.00326 ± 0.005209	0.00600 ± 99999	0.00100 ± 0.002828
RE: Change at Day 7 (n=8, 9, 9, 0, 6)	0.00935 ± 0.010193	0.00739 ± 0.005278	0.00460 ± 0.002929	99999 ± 99999	0.06128 ± 0.133660
HeT: Change at Day 1, 3h (n=7, 8, 6, 1, 7)	-0.0080 ± 0.02867	-0.0174 ± 0.02573	-0.0080 ± 0.01694	0.0000 ± 99999	0.0093 ± 0.01129
HeT: Change at Day 1, 7h (n=7, 8, 6, 2, 6)	-0.0011 ± 0.01935	0.0011 ± 0.01618	-0.0113 ± 0.04131	0.0215 ± 0.02616	-0.0418 ± 0.10265
HeT: Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	0.0460 ± 99999	99999 ± 99999	0.0060 ± 99999
HeT: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.0450 ± 99999
HeT: Change at Day 7 (n=17, 16, 12, 0, 16)	0.0144 ± 0.02895	0.0079 ± 0.02734	0.0241 ± 0.01695	99999 ± 99999	-0.0079 ± 0.06638
B/LU: Change at Day 1, 3h (n=5, 6, 4, 0, 4)	-0.0002 ± 0.00383	-0.0015 ± 0.01131	0.0030 ± 0.00469	99999 ± 99999	0.0020 ± 0.00542
B/LU: Change at Day 1, 7h (n=4, 5 ,5 ,1 ,3)	-0.0012 ± 0.00660	0.0018 ± 0.00349	-0.0014 ± 0.00488	0.0019 ± 99999	-0.0047 ± 0.00503
B/LU: Change at Day 3 (n=0, 0, 1, 0 ,1)	99999 ± 99999	99999 ± 99999	0.0000 ± 99999	99999 ± 99999	0.0000 ± 99999
B/LU: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.0030 ± 99999
B/LU: Change at Day 7 (n=9, 10, 9, 1, 7)	-0.0012 ± 0.00891	-0.0006 ± 0.01015	-0.0003 ± 0.00819	99999 ± 99999	-0.0020 ± 0.00693
E/LU: Change at Day 1, 3h (n=5, 6, 4, 0, 4)	0.0016 ± 0.00568	-0.0046 ± 0.01604	-0.0030 ± 0.00476	99999 ± 99999	0.0038 ± 0.01377
E/LU:Change at Day 1, 7h (n=4, 5, 5, 1, 3)	0.0055 ± 0.00971	-0.0022 ± 0.01291	-0.0008 ± 0.00719	0.0040 ± 99999	-0.0080 ± 0.00721
E/LU:Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	-0.0100 ± 99999	99999 ± 99999	0.0000 ± 99999
E/LU: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.0240 ± 99999
E/LU: Change at Day 7 (n=9, 10, 9, 0, 7)	0.0296 ± 0.02785	0.0198 ± 0.01600	0.0186 ± 0.01388	99999 ± 99999	0.0209 ± 0.02014
MO/LU:Change at Day 1, 3h (n=5, 6, 4, 0, 4)	-0.0156 ± 0.02907	-0.0075 ± 0.02661	-0.0573 ± 0.07671	99999 ± 99999	0.0065 ± 0.05313
MO/LU:Change at Day 1, 7h (n=4, 5, 5, 1, 3)	-0.0320 ± 0.05655	-0.0122 ± 0.00907	-0.0314 ± 0.04378	0.0020 ± 99999	-0.0070 ± 0.02858
MO/LU: Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	-0.1200 ± 99999	99999 ± 99999	0.0600 ± 99999
MO/LU: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.0310 ± 99999
MO/LU: Change at Day 7 (n=9, 10, 9, 0, 7)	-0.0197 ± 0.04803	-0.0067 ± 0.03467	-0.0504 ± 0.05563	99999 ± 99999	0.0036 ± 0.04837
N/LU: Change at Day 1, 3h (n=5, 6, 4, 0, 4)	-0.0396 ± 0.12380	-0.0355 ± 0.06897	0.0120 ± 0.08459	99999 ± 99999	-0.0460 ± 0.14651
N/LU: Change at Day 1 7h (n=4, 5, 5, 1, 3)	-0.0568 ± 0.10584	0.0664 ± 0.06183	-0.0208 ± 0.07854	-0.0940 ± 99999	-0.0400 ± 0.01732
N/LU: Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	0.1800 ± 99999	99999 ± 99999	0.0300 ± 99999
N/LU: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.0910 ± 99999
N/LU: Change at Day 7 (n=9, 10, 9, 0, 7)	-0.1278 ± 0.19019	-0.0833 ± 0.14232	-0.0551 ± 0.15450	99999 ± 99999	-0.0284 ± 0.19168
Ly/LU: Change at Day 1, 3h (n=5, 6, 4, 0, 4)	0.0858 ± 0.12152	0.0668 ± 0.07582	0.052 ± 0.04582	99999 ± 99999	0.0363 ± 0.10796
Ly/LU: Change at Day, 7h (n=4, 5, 5, 1, 3)	0.0945 ± 0.05695	-0.0500 ± 0.03889	0.052 ± 0.07604	0.0870 ± 99999	0.0997 ± 0.06603
Ly/LU: Change at Day 3 (n=0, 0, 1 ,0 ,1)	99999 ± 99999	99999 ± 99999	-0.0500 ± 99999	99999 ± 99999	0.0900 ± 99999
Ly/LU: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.3050 ± 99999
Ly/LU: Change at Day 7 (n=9, 10, 9, 0, 7)	0.1458 ± 0.17418	0.0731 ± 0.12663	0.0856 ± 0.19524	99999 ± 99999	-0.0611 ± 0.29588

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin)

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End point title

SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin) ^[27] ^[28]

End point description

Change from baseline for hematology- Erythrocytes Mean Corpuscular Hemoglobin was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline to Day 1, 3, 6 and Day 7

Notes
[27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Picogram (pg)
arithmetic mean (standard deviation)
Change at Day 1, 3h Postdose(n=7, 8, 7, 1, 7)	-0.286 ± 0.3934	-0.175 ± 0.5800	0.200 ± 0.3786	-0.400 ± 99999	-0.300 ± 0.5000
Change at Day 1, 7h postdose(n=7, 8, 6, 2, 6)	0.000 ± 0.5715	-0.137 ± 0.7050	0.017 ± 0.8377	-0.100 ± 0.1414	0.067 ± 0.7633
Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	0.000 ± 99999	99999 ± 99999	-0.700 ± 99999
Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.500 ± 99999
Change at Day 7 (n=17, 16, 12, 0, 16)	-0.347 ± 0.6829	-0.531 ± 0.7319	-0.233 ± 0.4979	99999 ± 99999	-0.269 ± 0.5606

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration)

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End point title

SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration) ^[29] ^[30]

End point description

Change from baseline in Hematology- Erythrocytes mean corpuscular HGB concentration was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

Baseline, Day 1, 3, 6 and Day 7

Notes
[29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Gram per liter (g/L)
arithmetic mean (standard deviation)
Change at Day 1, 3h Postdose (n=6, 8, 7, 1, 6)	-1.000 ± 4.1952	1.500 ± 7.7275	6.571 ± 10.3418	8.000 ± 99999	-2.333 ± 8.9815
Change at Day 1 7h, Postdose (n=5, 6, 6, 1, 5)	4.600 ± 11.6533	0.167 ± 6.1455	4.167 ± 10.9985	0.000 ± 99999	-0.200 ± 7.8867
Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	-3.000 ± 99999	99999 ± 99999	-7.000 ± 99999
Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-6.000 ± 99999
Change at Day 7 (15, 13, 12, 0, 13)	1.533 ± 10.7562	2.462 ± 10.6819	1.417 ± 10.3173	99999 ± 99999	-0.769 ± 7.9073

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology: Erythrocytes Mean Corpuscular Volume [e-MCV] and Mean Platelet Volume [MPV])

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End point title

SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology: Erythrocytes Mean Corpuscular Volume [e-MCV] and Mean Platelet Volume [MPV]) ^[31] ^[32]

End point description

Change from baseline in hematology: e-MCV and MPV were assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline to Day 1, 3, 6 and Day 7

Notes
[31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: femtolitre (fL)
arithmetic mean (standard deviation)
e-MCV:Change at Day 1, 3h Postdose(n=7,8,6,1,7)	-0.357 ± 1.5306	-0.862 ± 0.7210	-0.717 ± 1.3091	0.700 ± 99999	-0.271 ± 0.8180
e-MCV:Change at Day 1, 7h Postdose(n=7,8,6,2,6)	-0.529 ± 2.4150	-0.875 ± 1.0320	-1.017 ± 1.2906	0.000 ± 0.0000	-0.250 ± 0.7369
e-MCV: Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	0.600 ± 99999	99999 ± 99999	-0.600 ± 99999
e-MCV: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.000 ± 99999
e-MCV: Change at Day 7 (n=17, 16, 11, 0, 16)	-1.229 ± 1.7054	-2.213 ± 2.0803	-0.582 ± 1.4925	99999 ± 99999	-0.669 ± 1.7895
MPV: Change at Day 1, 3h Postdose(n=5, 5, 5, 0, 4)	0.080 ± 0.4324	-0.110 ± 0.2302	-1.020 ± 2.7022	99999 ± 99999	0.025 ± 0.7805
MPV: Change at Day 1, 7h Postdose(n=5, 4, 6, 2, 3)	-0.246 ± 1.0581	0.125 ± 0.8016	0.117 ± 0.7468	0.755 ± 0.3606	-0.140 ± 1.2770
MPV: Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	0.400 ± 99999	99999 ± 99999	-0.400 ± 99999
MPV: Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.600 ± 99999
MPV: Change at Day 7 (n=12, 9, 11, 0, 9)	-0.078 ± 0.8480	0.168 ± 0.7649	-0.509 ± 1.6202	99999 ± 99999	-0.212 ± 0.5398

No statistical analyses for this end point

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology: Erythrocytes Distribution Width)

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End point title

SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology: Erythrocytes Distribution Width) ^[33] ^[34]

End point description

Change from baseline for hematology: erythrocytes distribution width was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline to Day 1, 3, 6 and Day 7

Notes
[33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	18	14	3	17
Units: Percentage (%)
arithmetic mean (standard deviation)
Change at Day 1, 3h Postdose(n=5, 7, 4 ,0, 4)	0.020 ± 0.1095	0.100 ± 0.2309	0.350 ± 1.1030	99999 ± 99999	0.450 ± 0.3697
Change at Day 1, 7h Postdose(n=5, 5, 6, 1, 3)	0.700 ± 0.6595	0.180 ± 0.4919	0.700 ± 1.1243	0.800 ± 99999	0.333 ± 0.5774
Change at Day 3 (n=0, 0, 1, 0, 1)	99999 ± 99999	99999 ± 99999	0.300 ± 99999	99999 ± 99999	0.200 ± 99999
Change at Day 6 (n=0, 0, 0, 0, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.800 ± 99999
Change at Day 7 (n=12, 11, 10, 0, 9)	0.325 ± 0.6621	0.145 ± 0.5298	0.640 ± 1.0906	99999 ± 99999	0.233 ± 0.4873

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Physical Examination (Temperature)

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End point title

MAD: Change From Baseline in Physical Examination (Temperature) ^[35] ^[36]

End point description

End point type

Primary

End point timeframe

From Baseline up to Day 28

Notes
[35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: Degree Celsius
arithmetic mean (standard deviation)
Change at Day 1 (n=5,14,6,16,17,16,33)	-0.4 ± 1.35	-0.1 ± 0.81	-0.0 ± 0.37	-0.2 ± 0.86	-0.3 ± 0.74	-0.3 ± 0.84	-0.2 ± 0.66
Change at Day 2 (n=5 14, 6, 16, 16, 16, 33)	-0.8 ± 1.33	-0.1 ± 0.80	-0.3 ± 0.39	-0.0 ± 0.65	-0.5 ± 0.82	-0.3 ± 0.86	-0.2 ± 0.74
Change at Day 3 (n=5, 12, 6, 13, 14, 13, 27)	-0.4 ± 1.46	-0.1 ± 0.50	-0.5 ± 0.60	-0.2 ± 0.75	-0.6 ± 0.78	-0.7 ± 0.89	-0.4 ± 0.66
Change at Day 4 (n=5, 9, 4, 10, 8, 10, 22)	-0.2 ± 1.34	-0.1 ± 0.62	-0.6 ± 0.57	-0.5 ± 0.63	-0.7 ± 0.53	-0.8 ± 0.74	-0.4 ± 0.68
Change at Day 5 (n=5, 14, 6, 16, 15, 16, 31)	-0.8 ± 1.28	-0.4 ± 0.95	-0.4 ± 0.58	-0.4 ± 0.59	-0.6 ± 1.01	-0.6 ± 0.74	-0.3 ± 0.69
Change at Day 6 (n=3, 6, 4, 7, 5, 4, 8)	-0.5 ± 1.12	0.0 ± 0.64	-0.7 ± 0.43	-0.4 ± 0.61	-0.8 ± 0.94	-0.6 ± 0.56	-0.4 ± 0.41
Change at Day 7 (n=3, 4, 1, 5, 2, 2, 3)	-0.5 ± 0.59	0.1 ± 0.87	-0.5 ± 99999	-0.2 ± 0.65	-0.8 ± 0.64	-1.0 ± 0.71	-0.5 ± 0.55
Change at Day 8 (n=2, 3, 0, 3, 2, 0, 1)	-0.8 ± 1.06	-0.3 ± 0.36	99999 ± 99999	-1.2 ± 1.70	-0.7 ± 0.42	99999 ± 99999	0.2 ± 99999
Change at Day 9 (n=2, 2, 0, 1, 0, 0, 1)	-1.0 ± 0.78	-0.0 ± 0.07	99999 ± 99999	-0.2 ± 99999	99999 ± 99999	99999 ± 99999	0.2 ± 99999
Change at Day 10 (n=1, 1, 0, 0, 0, 0, 0)	-0.2 ± 99999	-0.2 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Change at Day 11 (n=5, 14, 5, 16, 18, 15, 32)	-0.8 ± 0.93	-0.3 ± 0.79	-0.4 ± 0.33	-0.6 ± 0.60	-0.7 ± 0.75	-0.8 ± 1.01	-0.4 ± 0.51
Change at Day 28 (n=4, 5, 1, 10, 10, 13, 17)	-1.2 ± 1.04	-0.1 ± 0.43	-0.2 ± 99999	-0.4 ± 0.54	-0.4 ± 0.65	-0.4 ± 0.98	-0.4 ± 0.74

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Physical Examination (Respiratory Rate)

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End point title

MAD: Change From Baseline in Physical Examination (Respiratory Rate) ^[37] ^[38]

End point description

End point type

Primary

End point timeframe

From Baseline up to Day 28

Notes
[37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: Breadth per minute
arithmetic mean (standard deviation)
Change at Day 1 (n=5,14,7,17,17,16,33)	-0.6 ± 21.02	0.7 ± 7.52	-7.6 ± 7.72	0.4 ± 10.07	-0.1 ± 9.80	-3.1 ± 13.02	-1.4 ± 11.16
Change at Day 2 (n=5, 14, 7, 17, 16, 16, 33)	-6.2 ± 9.76	-3.1 ± 12.09	-9.0 ± 8.04	-1.3 ± 7.95	-4.1 ± 14.01	-0.6 ± 15.84	0.7 ± 11.93
Change at Day 3 (n=5, 12, 6, 13, 14, 13, 27)	-5.4 ± 11.22	-5.8 ± 11.36	-9.7 ± 11.04	-1.7 ± 9.10	-6.4 ± 10.51	-6.7 ± 16.07	-4.0 ± 9.62
Change at Day 4 (n=5, 8, 5, 10, 7, 10, 22)	-9.8 ± 5.12	-12.0 ± 16.65	-8.0 ± 8.22	-2.6 ± 12.92	-6.9 ± 11.13	-10.6 ± 10.71	-4.9 ± 9.20
Change at Day 5 (n=5, 13, 7, 17, 15, 16, 32)	-8.2 ± 11.63	-8.9 ± 15.39	-8.1 ± 7.90	-3.6 ± 12.90	-4.5 ± 13.31	-6.9 ± 10.83	-0.8 ± 11.25
Change at Day 6 (n=3, 5, 4, 7, 4, 4, 8)	-3.7 ± 7.23	3.0 ± 6.60	-9.3 ± 16.72	-1.1 ± 3.98	-11.3 ± 7.09	-8.5 ± 9.57	-4.1 ± 8.59
Change at Day 7 (n=3, 3, 1, 5, 2, 2, 4)	-9.7 ± 11.68	-5.7 ± 21.55	10.0 ± 99999	-7.0 ± 3.16	-7.0 ± 18.38	-1.0 ± 9.90	3.3 ± 8.81
Change at Day 8 (n=2, 3, 0, 3, 2, 0, 1)	-6.5 ± 7.78	-5.0 ± 16.52	99999 ± 99999	-2.0 ± 19.29	-8.0 ± 16.97	99999 ± 99999	2.0 ± 99999
Change at Day 9 (n=2, 2, 0, 1, 0, 0, 1)	-7.5 ± 14.85	-2.5 ± 2.12	99999 ± 99999	-20.0 ± 99999	99999 ± 99999	99999 ± 99999	0.0 ± 99999
Change at Day 10 (1, 1, 0, 0, 0, 0, 0)	15.0 ± 99999	-4.0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Change at Day 11 (n=5, 14, 7, 17, 18, 15, 32)	-6.2 ± 9.15	-8.7 ± 17.98	-2.1 ± 13.06	-2.1 ± 12.64	-5.8 ± 12.24	-7.9 ± 13.53	-4.3 ± 12.60
Change at Day 28 (n= 3, 4, 2, 11, 10, 12, 20)	1.3 ± 4.73	2.8 ± 17.25	-0.5 ± 9.19	-4.3 ± 14.40	-8.4 ± 11.54	-9.7 ± 15.82	-3.9 ± 11.32

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Physical Examination (Heart Rate)

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End point title

MAD: Change From Baseline in Physical Examination (Heart Rate) ^[39] ^[40]

End point description

End point type

Primary

End point timeframe

From Baseline up to Day 28

Notes
[39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: Beats per minute
arithmetic mean (standard deviation)
Change at Day 1 (n=5,14,8,17,17,16,33)	-10.6 ± 21.03	-0.9 ± 21.63	-2.0 ± 14.80	8.2 ± 16.70	-1.4 ± 21.03	-6.4 ± 27.97	-0.6 ± 21.36
Change at Day 2 (n=5, 14, 8, 17, 16, 16, 33)	-12.2 ± 24.41	-2.3 ± 24.41	0.4 ± 26.09	2.0 ± 19.94	-5.8 ± 23.41	-4.2 ± 28.11	-6.2 ± 24.92
Change at Day 3 (n=5, 12, 7, 13, 14, 13, 27)	0.4 ± 23.42	-5.2 ± 12.26	-19.3 ± 31.49	-1.7 ± 19.55	-5.7 ± 22.28	-20.4 ± 24.80	-11.0 ± 31.19
Change at Day 4 (n=5, 9, 5, 10, 8, 10, 22)	-15.4 ± 35.51	-4.9 ± 23.12	-5.2 ± 29.08	-10.2 ± 34.27	-3.5 ± 14.49	-22.8 ± 25.12	-13.2 ± 19.49
Change at Day 5 (n=5, 14, 8, 17, 15, 16, 32)	-19.0 ± 23.46	-2.8 ± 24.45	-1.1 ± 24.17	-6.5 ± 21.95	-7.1 ± 27.62	-11.6 ± 27.46	-8.2 ± 27.01
Change at Day 6 (n=3, 6, 4, 7, 4, 4, 8)	-21.0 ± 26.23	4.7 ± 25.33	-13.3 ± 18.86	-8.0 ± 20.29	-30.0 ± 16.25	-7.0 ± 11.60	-15.3 ± 17.30
Change at Day 7 (n=3, 4, 1, 5, 2, 2, 4)	-17.0 ± 20.22	11.8 ± 16.64	-9.0 ± 99999	-14.2 ± 12.70	-2.0 ± 2.83	-15.0 ± 9.90	-4.0 ± 33.85
Change at Day 8 (n=2, 4, 0, 3, 2, 0, 1)	-24.5 ± 2.12	2.5 ± 20.50	99999 ± 99999	-10.3 ± 22.14	-32.0 ± 5.66	99999 ± 99999	-18.0 ± 99999
Change at Day 9 (n=2, 2, 0, 1, 0, 0, 1)	-6.5 ± 16.26	-8.0 ± 5.66	99999 ± 99999	14.0 ± 99999	99999 ± 99999	99999 ± 99999	-26.0 ± 99999
Change at Day 10 (n=1, 1, 0, 0, 0, 0, 0)	-13.0 ± 99999	3.0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Change at Day 11 (n=5, 14, 8, 17, 18, 15, 32)	-20.0 ± 23.19	-5.2 ± 24.71	6.3 ± 24.42	-6.9 ± 27.88	-1.3 ± 21.37	-17.3 ± 29.39	-6.8 ± 22.46
Change at Day 28 (n=4, 5, 2, 11, 11, 12, 20)	-17.5 ± 22.58	7.6 ± 23.04	-27.0 ± 22.63	-8.5 ± 23.75	-13.2 ± 21.61	-30.1 ± 30.53	-11.0 ± 26.38

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Physical Examination (Weight)

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End point title

MAD: Change From Baseline in Physical Examination (Weight) ^[41] ^[42]

End point description

Change from Baseline in weight was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline, Day 2, 5 and Day 28

Notes
[41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: Kilogram (kg)
arithmetic mean (standard deviation)
Change at Day 2 12h (n=5, 13, 7, 17, 15, 14 ,31)	0.1 ± 0.28	0.0 ± 0.25	0.1 ± 0.11	-0.1 ± 0.23	0.2 ± 0.29	0.0 ± 0.18	0.1 ± 0.39
Change at Day 5 (n=5, 14, 6, 15, 15, 15, 30)	0.1 ± 0.31	0.0 ± 0.22	0.0 ± 0.10	-0.0 ± 0.28	0.0 ± 0.21	-0.0 ± 0.38	0.0 ± 0.18
Change at Day 28 (n=5, 14, 8, 16, 16, 15, 31)	0.6 ± 0.32	0.5 ± 0.44	0.8 ± 0.31	0.6 ± 0.44	0.7 ± 0.34	0.7 ± 0.40	0.6 ± 0.40

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Physical Examination (BMI)

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End point title

MAD: Change From Baseline in Physical Examination (BMI) ^[43] ^[44]

End point description

Change from baseline in BMI was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline, Day 2, 5 and Day 28

Notes
[43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: kg/m^2
arithmetic mean (standard deviation)
Change at Day 2 12h (n=5, 12, 7, 17, 15, 14 ,31)	0.4 ± 0.61	0.1 ± 0.67	0.2 ± 0.29	-0.2 ± 0.68	0.4 ± 0.64	0.1 ± 0.45	0.4 ± 1.39
Change at Day 5 (n=5, 13, 6, 15, 15, 14, 30)	0.3 ± 0.67	0.1 ± 0.72	0.0 ± 0.26	-0.1 ± 0.84	0.1 ± 0.46	-0.0 ± 0.82	0.2 ± 0.64
Change at Day 28 (n=5, 13, 8, 16, 16, 14, 31)	1.5 ± 0.94	1.6 ± 1.54	2.4 ± 1.27	1.6 ± 1.35	1.7 ± 1.00	1.9 ± 1.22	2.0 ± 1.44

No statistical analyses for this end point

Primary: MAD: Change From Baseline for Vital signs (Blood Pressure: sBP and dBP)

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End point title

MAD: Change From Baseline for Vital signs (Blood Pressure: sBP and dBP) ^[45] ^[46]

End point description

Change from Baseline in Blood pressure: sBP and dBP was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline to Day 28

Notes
[45] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: mmHg
arithmetic mean (standard deviation)
sBP: Change at Day 1 (n=5,5,3,2,6,6,11)	1.6 ± 12.62	0.6 ± 19.46	6.0 ± 8.72	5.0 ± 7.07	0.8 ± 7.60	8.0 ± 15.38	-3.1 ± 16.20
sBP: Change at Day 2 (n=5, 5, 3, 2, 5, 6, 11)	8.8 ± 9.09	-2.0 ± 13.84	11.3 ± 6.43	9.0 ± 9.90	-3.0 ± 11.51	7.5 ± 12.50	1.8 ± 18.15
sBP: Change at Day 3 (n= 5, 5, 3, 2, 3, 6, 11)	3.8 ± 8.23	3.6 ± 18.51	6.3 ± 12.66	19.5 ± 6.36	3.4 ± 23.31	4.7 ± 13.65	6.5 ± 16.11
sBP: Change at Day 4 (n=5, 5, 3, 2, 5, 6, 11)	14.0 ± 30.14	-4.0 ± 19.71	10.7 ± 17.47	11.0 ± 12.73	-3.3 ± 12.10	4.5 ± 15.67	-3.6 ± 14.81
sBP: Change at Day 5 (n=5, 5, 3, 2, 5, 6, 11)	7.8 ± 7.98	7.4 ± 20.27	13.7 ± 20.40	16.5 ± 17.68	7.0 ± 17.65	-0.3 ± 20.16	3.5 ± 16.59
sBP: Change at Day 6 (n=3, 4, 3, 1, 2, 3, 6)	-0.3 ± 9.50	-1.0 ± 12.27	6.7 ± 9.24	5.0 ± 99999	1.5 ± 10.61	-4.7 ± 14.36	1.5 ± 21.71
sBP: Change at Day 7 (n=3, 2, 0, 0, 1, 1, 2)	3.0 ± 13.00	-13.0 ± 21.21	99999 ± 99999	99999 ± 99999	-7.0 ± 99999	-10.0 ± 99999	6.5 ± 12.02
sBP: Change at Day 8 (n=2, 2, 0, 0, 1, 0, 1)	-5.5 ± 19.09	6.0 ± 22.63	99999 ± 99999	99999 ± 99999	13.0 ± 99999	99999 ± 99999	-2.0 ± 99999
sBP: Change at Day 9 (n=2, 2, 0, 0, 0, 0, 1)	1.5 ± 0.71	-0.5 ± 10.61	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	2.0 ± 99999
sBP: Change at Day 10 (n=1, 1, 0, 0, 0, 0,0)	0.0 ± 99999	21.0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
sBP: Change at Day 11 (n=5, 5, 3, 2, 6, 6, 11)	1.2 ± 17.91	8.0 ± 23.32	1.0 ± 29.60	18.5 ± 14.85	-2.5 ± 22.90	-2.0 ± 9.59	3.7 ± 10.87
sBP: Change at Day 28 (n=4, 1, 0, 1, 1, 2, 5)	6.0 ± 19.20	-4.0 ± 99999	99999 ± 99999	14.0 ± 99999	15.0 ± 99999	2.0 ± 16.97	9.0 ± 17.52
dBP: Change at Day 1 (n=5,5,3,2,6,6,11)	-2.8 ± 14.27	-4.8 ± 14.18	6.7 ± 13.32	-1.5 ± 19.09	-2.7 ± 12.89	8.2 ± 14.96	-3.7 ± 8.20
dBP: Change at Day 2 (n=5, 5, 3, 2, 5, 6, 10)	-2.6 ± 15.26	-3.2 ± 11.19	3.3 ± 11.37	-8.0 ± 8.49	-2.6 ± 13.41	9.2 ± 9.04	-0.1 ± 10.04
dBP: Change at Day 3 (n= 5, 5, 3, 2, 5, 6, 11)	-5.2 ± 9.78	0.6 ± 22.53	-6.0 ± 5.29	13.0 ± 7.07	2.0 ± 14.42	7.0 ± 10.22	3.5 ± 9.35
dBP: Change at Day 4 (n=5, 5, 3, 2, 3, 6, 10)	-7.8 ± 24.20	-7.6 ± 10.92	6.0 ± 5.29	3.0 ± 15.56	4.3 ± 10.02	9.2 ± 19.92	0.1 ± 11.31
dBP: Change at Day 5 (n=5, 5, 3, 2, 5, 6, 10)	-8.0 ± 16.00	7.4 ± 14.38	7.3 ± 9.87	4.0 ± 8.49	-1.8 ± 14.87	5.0 ± 22.61	3.0 ± 14.61
dBP: Change at Day 6 (n=3, 4, 3, 1, 2, 3, 6)	-2.7 ± 8.33	-10.0 ± 11.34	4.7 ± 6.11	2.0 ± 99999	-6.5 ± 13.44	-15.7 ± 9.61	2.8 ± 8.47
dBP: Change at Day 7 (n=3, 2, 0, 0, 1, 1, 2)	-12.7 ± 11.02	-15.5 ± 3.54	99999 ± 99999	99999 ± 99999	12.0 ± 99999	4.0 ± 99999	-4.0 ± 4.24
dBP: Change at Day 8 (n=2, 2, 0, 0, 1, 0, 1)	-6.0 ± 2.83	-7.0 ± 43.84	99999 ± 99999	99999 ± 99999	4.0 ± 99999	99999 ± 99999	0.0 ± 99999
dBP: Change at Day 9 (n=2, 2, 0, 0, 0, 0, 1)	-4.0 ± 11.31	-8.5 ± 0.71	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	9.0 ± 99999
dBP: Change at Day 10 (n=1, 1, 0, 0, 0, 0,0)	-4.0 ± 99999	-7.0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
dBP: Change at Day 11 (n=5, 5, 3, 2, 6, 6, 10)	-3.8 ± 9.63	11.8 ± 27.58	-9.0 ± 10.82	7.5 ± 6.36	3.2 ± 13.17	11.2 ± 17.13	2.7 ± 10.58
dBP: Change at Day 28 (n=4, 1, 0, 1, 1, 2, 4)	-6.3 ± 9.81	-19.0 ± 99999	99999 ± 99999	-7.0 ± 99999	-27.0 ± 99999	5.0 ± 25.46	16.5 ± 10.41

No statistical analyses for this end point

Primary: MAD: Change From Baseline in ECG Parameters

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End point title

MAD: Change From Baseline in ECG Parameters ^[47] ^[48]

End point description

Change from Baseline in ECG parameters (RR interval, PR interval, QRS interval, QT interval, QTcB interval, QTcF interval) was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline, Day 1, 5, 11 and Day 28

Notes
[47] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: msec
arithmetic mean (standard deviation)
RR:Change at Day 1 (n=5,13,8,17,17,16,32)	-34.4 ± 95.16	11.6 ± 58.91	-12.3 ± 77.26	-12.6 ± 54.18	-8.9 ± 70.07	8.3 ± 57.33	4.8 ± 51.96
RR:Change at Day 5 (n=5, 14, 8, 16, 15, 15, 33)	37.2 ± 91.58	-15.8 ± 110.61	-32.0 ± 93.81	-0.2 ± 80.67	29.3 ± 64.02	23.9 ± 74.62	5.9 ± 79.53
RR:Change at Day 11 (n=5, 14, 8, 16, 17, 15, 32)	-10.0 ± 51.79	13.7 ± 65.29	-23.1 ± 62.18	-18.0 ± 114.64	30.9 ± 72.50	32.6 ± 64.66	9.0 ± 78.18
RR:Change at Day 28 (n=2, 3, 0, 3, 0, 1, 3)	1.0 ± 43.84	-3.3 ± 68.16	99999 ± 99999	32.0 ± 30.41	99999 ± 99999	0.0 ± 99999	68.3 ± 84.24
PR:Change at Day 1 (n=5,14,8,15,17,15,31)	12.0 ± 14.70	3.3 ± 8.41	-12.1 ± 41.51	7.0 ± 33.16	-4.6 ± 11.23	2.9 ± 12.59	0.2 ± 17.89
PR:Change at Day 5 (n=5, 12, 8, 16, 15, 14, 32)	-4.4 ± 21.00	4.2 ± 6.69	-15.6 ± 35.96	5.3 ± 30.86	6.2 ± 14.17	6.3 ± 19.72	-2.0 ± 13.74
PR:Change at Day 11 (n=5, 14, 8, 15, 16, 14, 31)	-5.6 ± 14.38	-1.1 ± 15.21	-14.9 ± 35.69	-2.6 ± 19.59	-1.3 ± 13.58	-2.4 ± 15.72	-4.0 ± 17.13
PR:Change at Day 28 (n=2, 3, 0, 3, 0, 1, 3)	-1.0 ± 7.07	0.0 ± 24.25	99999 ± 99999	-6.3 ± 15.50	99999 ± 99999	0.0 ± 99999	19.0 ± 12.77
QRS:Change at Day 1 (n=5,14,8,17,17,16,32)	3.6 ± 4.10	-1.0 ± 5.31	-0.8 ± 3.41	-4.5 ± 28.49	0.6 ± 2.45	-2.6 ± 13.03	-0.5 ± 5.87
QRS:Change at Day 5 (n=5, 14, 8, 16, 15, 15, 33)	4.4 ± 3.29	-0.3 ± 4.21	-0.5 ± 5.01	-5.5 ± 29.01	-2.6 ± 6.76	-1.8 ± 11.81	-1.0 ± 6.07
QRS:Change at Day 11 (n=5, 14, 8, 16, 17, 15, 32)	7.2 ± 4.60	0.5 ± 7.22	-1.9 ± 3.72	-5.6 ± 24.57	0.5 ± 6.94	-2.8 ± 14.85	0.9 ± 8.50
QRS:Change at Day 28 (n=2, 3, 0, 3, 0, 1, 3)	7.0 ± 4.24	1.3 ± 3.06	99999 ± 99999	-56.0 ± 55.03	99999 ± 99999	-40.0 ± 99999	4.3 ± 2.08
QT: Change at Day 1 (n=5,14,8,17,17,16,32)	-12.4 ± 35.76	-0.2 ± 14.62	-4.0 ± 20.26	4.8 ± 29.09	7.8 ± 24.57	7.4 ± 35.45	-8.4 ± 33.65
QT:Change at Day 5 (n=5, 14, 8, 16, 15, 15, 33)	27.2 ± 43.14	4.1 ± 27.13	-19.3 ± 22.52	1.2 ± 29.00	2.3 ± 29.47	10.9 ± 40.16	3.9 ± 48.75
QT:Change at Day 11 (n=5, 14, 8, 16, 17, 15, 32)	16.8 ± 34.43	1.9 ± 22.62	-11.8 ± 11.47	6.6 ± 36.29	10.2 ± 31.61	16.0 ± 41.38	-1.7 ± 34.84
QT:Change at Day 28 (n=2, 3, 0, 3, 0, 1, 3)	10.0 ± 14.14	0.7 ± 34.49	99999 ± 99999	84.3 ± 89.61	99999 ± 99999	-20.0 ± 99999	33.7 ± 29.87
QTcB:Change at Day 1 (n=5,14,8,17,17,16,32)	-1.6 ± 12.40	-6.1 ± 21.58	-4.4 ± 22.08	17.9 ± 25.50	16.9 ± 48.69	8.1 ± 59.41	-15.9 ± 39.99
QTcB:Change at Day 5 (n=5, 14, 8, 16, 15, 15, 33)	23.6 ± 64.75	-5.7 ± 21.79	-15.4 ± 34.21	4.3 ± 26.53	-13.8 ± 48.84	3.3 ± 51.19	-5.1 ± 35.99
QTcB:Change at Day 11 (n=5, 14, 8, 16, 17, 15, 32)	32.4 ± 51.49	-4.6 ± 27.31	-7.3 ± 40.56	5.9 ± 33.87	1.3 ± 38.42	7.6 ± 51.09	-8.2 ± 46.59
QTcB:Change at Day 28 (n=2, 3, 0, 3, 0, 1, 3)	12.0 ± 0.00	2.3 ± 38.19	99999 ± 99999	34.3 ± 32.15	99999 ± 99999	-31.0 ± 99999	16.0 ± 7.00
QTcF:Change at Day 1 (n=5,14,8,17,17,16,32)	-6.8 ± 21.04	-6.6 ± 23.23	-4.3 ± 16.99	12.5 ± 24.98	12.2 ± 34.86	8.5 ± 48.11	-12.8 ± 36.53
QTcF:Change at Day 5 (n=5, 14, 8, 16, 15, 15, 33)	25.2 ± 53.02	-5.4 ± 19.29	-17.6 ± 22.33	2.4 ± 25.08	-6.9 ± 39.59	7.3 ± 44.38	-3.4 ± 34.16
QTcF:Change at Day 11 (n=5, 14, 8, 16, 17, 15, 32)	25.8 ± 43.59	-3.8 ± 28.90	-10.3 ± 28.62	5.6 ± 33.59	5.4 ± 33.35	21.7 ± 57.05	-5.4 ± 39.06
QTcF:Change at Day 28 (n=2, 3, 0, 3, 0, 1, 3)	11.5 ± 6.36	-12.7 ± 52.63	99999 ± 99999	26.3 ± 37.17	99999 ± 99999	-20.0 ± 99999	24.3 ± 15.89

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter: Serum Chemistry-Alkaline Phosphatase (AP), Alanine Aminotransferase (ALA), Aspartate Aminotransferase (ASA), Creatine Kinase (CrK)

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End point title

MAD: Change From Baseline in Clinical Laboratory Parameter: Serum Chemistry-Alkaline Phosphatase (AP), Alanine Aminotransferase (ALA), Aspartate Aminotransferase (ASA), Creatine Kinase (CrK) ^[49] ^[50]

End point description

Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-AP, ALA, ASA, CrK) was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline, Day 1, 3, 4, 5, 6, 7, 11 and 28

Notes
[49] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: ukat/L
arithmetic mean (standard deviation)
AP: Change at Day 1 (n=3,6,5,9,8,8,15)	-1.678 ± 3.5728	-0.564 ± 0.9252	-0.050 ± 0.8050	-0.219 ± 0.8755	-0.656 ± 1.5735	-1.386 ± 1.1609	-0.961 ± 1.2125
AP: Change at Day 1 7h (n=2, 8, 2, 7, 8, 7, 15)	-0.008 ± 1.3320	-0.438 ± 0.6512	-1.367 ± 2.2160	-0.402 ± 0.8138	-0.208 ± 0.4361	-0.143 ± 0.2834	-0.412 ± 0.8993
AP: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 1)	99999 ± 99999	-0.267 ± 99999	-0.133 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.250 ± 99999
AP: Change at Day 4 (n=0, 1, 0, 0, 0, 1, 1)	99999 ± 99999	-0.233 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.800 ± 99999	0.383 ± 99999
AP: Change at Day 5 (n=5, 14, 7, 15, 14, 15, 29)	0.333 ± 3.2360	0.120 ± 0.3483	0.414 ± 0.9106	-0.045 ± 0.5638	0.643 ± 1.1915	0.837 ± 1.8684	0.240 ± 1.3498
AP: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.333 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
AP: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-1.200 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
AP: Change at Day 11 (n=5, 14, 6, 15, 18, 15, 28)	2.934 ± 3.1704	0.805 ± 1.3344	0.856 ± 0.8769	0.396 ± 0.9444	1.335 ± 2.0936	2.153 ± 2.1544	1.294 ± 1.8375
AP: Change at Day 28 (n=4, 2, 2, 3, 1, 3, 3)	6.218 ± 2.9955	0.867 ± 0.2829	3.101 ± 2.7818	0.272 ± 0.2710	6.718 ± 99999	1.022 ± 1.1542	0.600 ± 0.1093
ALA: Change at Day 1 (n=3,6,5,9,8,8,15)	0.128 ± 0.2111	-0.056 ± 0.0880	0.007 ± 0.0325	0.016 ± 0.1814	0.044 ± 0.1324	-0.056 ± 0.0597	0.004 ± 0.0722
ALA: Change at Day 1 7h (n=2,8,3,7,8,8,15)	0.283 ± 0.3536	0.079 ± 0.3680	-0.006 ± 0.0822	-0.012 ± 0.0865	0.063 ± 0.0755	0.190 ± 0.2042	-0.038 ± 0.0803
ALA: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 1)	99999 ± 99999	-0.117 ± 99999	-0.050 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.033 ± 99999
ALA: Change at Day 4 (n=0, 1, 0, 0, 0, 1, 1)	99999 ± 99999	-0.117 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.000 ± 99999	0.117 ± 99999
ALA: Change at Day 5 (n=5, 14, 8, 16, 13, 15, 29)	0.273 ± 0.4086	0.057 ± 0.2540	0.113 ± 0.1195	0.021 ± 0.3011	0.210 ± 0.2255	0.248 ± 0.2658	0.039 ± 0.1429
ALA: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.083 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
ALA: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	0.167 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
ALA: Change at Day 11(n=5, 14, 7, 15, 18, 15, 29)	0.113 ± 0.2637	0.163 ± 0.4496	0.167 ± 0.3535	-0.037 ± 0.2464	0.146 ± 0.2115	0.039 ± 0.2169	0.006 ± 0.2091
ALA: Change at Day 28 (n=4, 2, 2, 3, 2, 4, 4)	0.075 ± 0.0739	0.017 ± 0.0236	0.292 ± 0.0354	-0.411 ± 0.4016	0.142 ± 0.2947	0.179 ± 0.3211	0.050 ± 0.0943
ASA: Change at Day 1 (n=3,4,5,9,8,8,13)	0.211 ± 0.2937	0.013 ± 0.1258	0.110 ± 0.1251	-0.074 ± 0.4793	0.104 ± 0.2739	-0.085 ± 0.0721	0.005 ± 0.0846
ASA: Change at Day 1 7h (n=2,8,3,7,8,8,15)	0.400 ± 0.6129	0.138 ± 0.4543	-0.022 ± 0.0347	-0.043 ± 0.2400	0.150 ± 0.2118	0.402 ± 0.4497	-0.122 ± 0.5006
ASA: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 1)	99999 ± 99999	-0.100 ± 99999	0.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.167 ± 99999
ASA: Change at Day 4 (n=0, 1, 0, 0, 0, 1, 1)	99999 ± 99999	-0.183 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.017 ± 99999	-0.133 ± 99999
ASA: Change at Day 5 (n=5, 12, 8, 16, 14, 15, 28)	0.137 ± 0.1891	0.089 ± 0.1865	0.113 ± 0.1558	-0.186 ± 0.3501	0.176 ± 0.2563	0.295 ± 0.3749	0.044 ± 0.5127
ASA: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.250 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
ASA: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	0.033 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
ASA: Change at Day 11 (n=5, 11, 7, 14, 18, 15, 26)	0.077 ± 0.0384	0.188 ± 0.3124	0.186 ± 0.1230	-0.092 ± 0.4864	0.184 ± 0.3527	0.120 ± 0.2835	-0.021 ± 0.5298
ASA: Change at Day 28 (n=4, 2, 2, 3, 3, 4, 4)	0.142 ± 0.1190	0.008 ± 0.0589	0.233 ± 0.0000	-0.706 ± 0.7171	0.267 ± 0.2892	0.142 ± 0.2197	-0.033 ± 0.1587
CrK: Change at Day 1 0.5-1h (n=3,6,5,6,6,8,16)	0.478 ± 0.7057	0.067 ± 0.4563	-0.173 ± 0.2965	1.147 ± 1.4385	-0.314 ± 0.8019	0.271 ± 1.7412	-0.058 ± 0.7089
CrK: Change at Day 1 7h (n=2,8,3,7,8,7,15)	-1.309 ± 2.3693	-0.394 ± 0.9921	-0.161 ± 0.2811	-0.619 ± 0.7937	0.381 ± 1.5252	0.257 ± 0.6124	0.190 ± 0.8554
CrK: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 0)	99999 ± 99999	-0.017 ± 99999	0.350 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
CrK: Change at Day 4 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	-0.400 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.583 ± 99999
CrK: Change at Day 5 (n=5, 14, 8, 13, 13, 15, 30)	-0.820 ± 1.8541	-0.201 ± 0.7061	-0.006 ± 0.4932	-0.126 ± 5.4970	0.276 ± 1.5585	-0.442 ± 0.7528	-0.251 ± 0.8541
CrK: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	-1.867 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
CrK: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	1.084 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
CrK: Change at Day 11(n=5, 14, 7, 13, 17, 15, 29)	0.160 ± 2.5623	0.418 ± 1.5535	0.445 ± 0.9954	-1.121 ± 3.3099	0.478 ± 1.5865	0.069 ± 0.9801	0.155 ± 1.0566
CrK: Change at Day 28 (n=4, 2, 2, 3, 2, 4, 5)	2.192 ± 1.2596	-0.142 ± 0.5304	1.234 ± 0.7072	0.111 ± 1.3676	-0.592 ± 0.4833	0.554 ± 0.8134	-0.200 ± 1.1625

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Bilirubin, Direct [DB], Indirect bilirubin [IB], and Creatinine [Cr])

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End point title

MAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Bilirubin, Direct [DB], Indirect bilirubin [IB], and Creatinine [Cr]) ^[51] ^[52]

End point description

Change from baseline in serum chemistry-bilirubin, DB, IB, and Cr were assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

For Bilirubin, DB and Cr: From Baseline, Day 1, 3, 4, 5, 6, 7, 11 and Day 28; For IB: From Baseline, Day 1, 5, 6, 11 and Day 28

Notes
[51] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: mcmol/L
arithmetic mean (standard deviation)
BI: Change at Day 1 (n=3,5,5,9,8,8,15)	-1.140 ± 3.3217	0.342 ± 1.4307	-3.078 ± 9.1609	3.227 ± 7.9231	-1.774 ± 4.8641	-4.147 ± 11.4866	-3.306 ± 7.5812
BI: Change at Day 1, 7h (n=2,6,3,6,8,8,14)	0.086 ± 2.2974	-11.681 ± 15.9198	-3.990 ± 0.9873	-0.570 ± 1.4334	-1.664 ± 1.8058	-0.792 ± 1.7033	-1.083 ± 2.5768
BI: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 1)	99999 ± 99999	-32.490 ± 99999	99999 ± 0.000	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.000 ± 99999
BI: Change at Day 4 (n=0, 1, 0, 0, 0, 1, 1)	99999 ± 99999	-32.490 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.000 ± 99999	-1.710 ± 99999
BI: Change at Day 5 (n=5, 11, 8, 15, 14, 15, 28)	-5.917 ± 18.2360	-7.604 ± 15.6519	-6.840 ± 17.3185	0.371 ± 2.1723	-0.020 ± 5.3325	-0.401 ± 9.9071	-4.395 ± 9.4563
BI: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	-1.710 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
BI: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-5.130 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
BI: Change at Day 11 (n=5,11,7,14,18,15,27)	-3.762 ± 16.0544	-9.749 ± 20.9100	-9.039 ± 23.1896	1.049 ± 3.0559	-4.482 ± 16.4250	-2.601 ± 13.6963	-3.483 ± 13.4190
BI: Change at Day 28 (n=4, 2, 2, 3, 2, 4, 3)	1.325 ± 4.3403	-29.412 ± 23.6994	-35.055 ± 47.1570	-0.473 ± 2.1420	-1.539 ± 0.2418	-56.644 ± 115.0046	-3.990 ± 3.5596
DB: Change at Day 1 (n=3,2,4,6,7,7,14)	-0.456 ± 0.5224	0.000 ± 0.0000	-1.282 ± 5.6499	-0.627 ± 2.2418	-1.026 ± 1.9144	-0.318 ± 1.0468	-0.794 ± 1.5551
DB: Change at Day 1 7h (n=1,3,2,4,7,5,13)	0.000 ± 99999	-3.534 ± 6.8514	0.000 ± 0.0000	0.299 ± 1.5191	-1.221 ± 1.1987	-0.068 ± 0.9413	-0.105 ± 1.2769
DB: Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	0.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	1.710 ± 99999
DB: Change at Day 4 (n=0, 1, 0, 0, 0, 1, 1)	99999 ± 99999	0.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.000 ± 99999
DB: Change at Day 5 (n=5, 5, 5, 11, 13, 12, 25)	0.239 ± 1.9482	-2.804 ± 5.2825	-4.104 ± 8.2542	-0.171 ± 1.9765	-0.460 ± 1.9775	0.114 ± 1.2186	-0.705 ± 1.7173
DB: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
DB: Change at Day 11 (n=5, 5, 5, 12, 15, 12, 24)	-0.376 ± 1.3913	-4.104 ± 8.0787	-4.104 ± 10.1598	0.128 ± 1.9252	0.091 ± 4.1060	-0.242 ± 1.3996	-0.477 ± 1.9627
DB: Change at Day 28 (n=4, 2, 2, 2, 2, 4, 3)	0.000 ± 1.3098	-1.197 ± 1.6928	-11.970 ± 16.9281	0.000 ± 0.0000	-1.026 ± 0.9673	0.256 ± 1.2051	-1.140 ± 0.9873
IB: Change at Day 1 (n=2,1,2,3,3,5,7)	-1.881 ± 2.6601	1.710 ± 99999	0.855 ± 1.2092	7.752 ± 14.2252	0.513 ± 0.4524	-6.532 ± 14.5141	-3.469 ± 9.1623
IB: Change at Day 1 7h (n=0,2,0,3,4,2,6)	99999 ± 99999	-14.279 ± 15.1144	99999 ± 99999	-0.627 ± 1.3927	0.342 ± 1.1513	-0.940 ± 3.7484	-0.940 ± 1.1933
IB: Change at Day 5 (n=3, 3, 2, 7, 7, 7, 13)	-1.710 ± 1.3356	-10.887 ± 16.5140	0.855 ± 1.2092	-0.489 ± 1.7197	2.028 ± 3.4078	-2.565 ± 13.5328	-3.065 ± 8.0289
IB: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	-1.710 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
IB: Change at Day 11 (n=3, 3, 2, 8, 7, 7, 13)	-1.083 ± 1.8758	-15.219 ± 24.4638	0.000 ± 2.4183	0.641 ± 3.0256	1.344 ± 1.2466	-5.667 ± 19.5016	-2.451 ± 10.6977
IB: Change at Day 28 (n=3, 1, 0, 0, 2, 4, 1)	0.057 ± 2.1517	-10.260 ± 99999	99999 ± 99999	99999 ± 99999	-0.513 ± 0.7255	-56.772 ± 114.9225	0.000 ± 99999
Cr: Change at Day 1 (n=3,6,5,9,8,8,16)	-0.589 ± 1.0208	0.609 ± 1.6200	-1.414 ± 2.3884	-0.295 ± 6.0649	1.989 ± 4.7193	-2.431 ± 2.5773	-1.602 ± 3.4042
Cr: Change at Day 1 7h (n=2,8,3,7,8,8,16)	0.442 ± 4.3756	-1.341 ± 1.6999	-4.420 ± 7.6557	1.894 ± 6.4443	1.303 ± 6.5106	1.475 ± 6.9183	-2.438 ± 8.0003
Cr: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 1)	99999 ± 99999	-7.956 ± 99999	-3.536 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	2.652 ± 99999
Cr: Change at Day 4 (n=0, 1, 0, 0, 0, 1, 1)	99999 ± 99999	-3.536 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-1.768 ± 99999	0.884 ± 99999
Cr: Change at Day 5 (n=5, 14, 8, 16, 14, 15, 32)	0.354 ± 1.4792	0.294 ± 4.1295	-0.331 ± 7.6620	0.077 ± 6.7179	1.439 ± 4.0210	-0.825 ± 4.1927	-1.005 ± 6.2223
Cr: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.884 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cr: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	0.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cr: Change at Day 11 (n=5, 13, 7, 14, 18, 15, 31)	-0.354 ± 2.3884	0.331 ± 2.8039	-2.526 ± 5.0892	-0.522 ± 7.4052	0.376 ± 5.0890	-1.002 ± 4.1445	-0.128 ± 6.5873
Cr: Change at Day 28 (n=4,2,2,4,2,4,4)	0.000 ± 2.9760	-5.746 ± 6.8759	-1.768 ± 5.0007	1.960 ± 8.4423	-1.326 ± 1.8752	3.978 ± 11.6942	3.757 ± 3.5635

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Blood Urea nitrogen [BUN], Derived Urea [DU], Chloride [Cl], Bicarbonate [BiC], Glucose [Glu], Potassium [K], Sodium [Na])

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End point title

MAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Blood Urea nitrogen [BUN], Derived Urea [DU], Chloride [Cl], Bicarbonate [BiC], Glucose [Glu], Potassium [K], Sodium [Na]) ^[53] ^[54]

End point description

Change From Baseline for Clinical Laboratory Parameter (Serum Chemistry-BUN, DU, Cl, BiC, Glu, K, and Na) was assessed. HeSafety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

For BUN, DU, Cl, Glu, K and Na: From Baseline Day 1, 3, 4, 5, 6, 7, 11 and Day 28; For BiC: From Baseline, Day 1, 3, 4, 5, 11 and Day 28

Notes
[53] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: mmol/L
arithmetic mean (standard deviation)
BUN: Change at Day 1, (n=3,4,5,7,8,8,16)	-0.464 ± 1.3674	-0.295 ± 0.8288	-0.143 ± 0.7403	-0.525 ± 0.7442	-0.469 ± 1.3102	-0.927 ± 1.4263	-0.512 ± 0.6770
BUN: Change at Day 1, 7h (n=2,5,3,7,7,6,13)	-0.286 ± 0.4039	-0.750 ± 0.5143	-0.952 ± 1.3516	0.092 ± 0.6537	-0.719 ± 1.4030	-0.286 ± 0.7147	-0.637 ± 0.8280
BUN: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 1)	99999 ± 99999	-0.536 ± 99999	1.071 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.964 ± 99999
BUN: Change at Day 4 (n=0, 1, 0, 0, 0, 1, 0)	99999 ± 99999	-0.428 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.714 ± 99999
BUN: Change at Day 5 (n=5, 9, 8, 13, 13, 15, 29)	0.086 ± 0.9876	-0.258 ± 0.9709	0.223 ± 1.6846	-0.014 ± 1.0222	0.232 ± 1.2653	0.322 ± 1.4978	0.057 ± 0.7834
BUN: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.643 ± 99999	99999 ± 99999	0.643 ± 99999	99999 ± 99999
BUN: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-0.500 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
BUN: Change at Day 11 (n=5, 8, 7, 13, 16, 15, 28)	0.307 ± 0.3494	0.884 ± 2.2140	0.408 ± 1.5066	0.719 ± 1.3786	0.364 ± 1.3144	0.501 ± 1.2024	0.395 ± 0.8645
BUN: Change at Day 28 (n=4, 2, 2, 3, 1, 4, 4)	0.598 ± 1.0962	0.196 ± 0.536	0.2524 ± 0.428	0.2574 ± 1.071	99999 ± 1.011	1.3398 ± 99999	0.446 ± 0.6262
DU: Change at Day 1 (n=3,6,5,9,8,8,16)	-0.464 ± 1.3674	-0.263 ± 0.6438	-0.143 ± 0.7403	-0.331 ± 0.7714	-0.674 ± 1.4148	-0.927 ± 1.4263	-0.574 ± 0.6728
DU: Change at Day 1 7h (n=2,7,3,7,8,7,15)	-0.286 ± 0.4039	-0.578 ± 0.6023	-0.952 ± 1.3516	0.092 ± 0.6537	-0.642 ± 1.3172	-0.331 ± 0.6632	-0.369 ± 1.4107
DU: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 1)	99999 ± 99999	-0.536 ± 99999	1.071 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.964 ± 99999
DU: Change at Day 4 (n=0, 1, 0, 0, 0, 1, 1)	99999 ± 99999	-0.428 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-1.714 ± 99999	0.714 ± 99999
DU: Change at Day 5 (n=5, 13, 8, 14, 14, 15, 32)	0.086 ± 0.9876	-0.048 ± 0.8651	0.223 ± 1.6846	0.052 ± 1.0120	0.859 ± 2.8693	0.322 ± 1.4978	0.007 ± 1.1992
DU: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.643 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
DU: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-0.500 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
DU: Change at Day 11 (n=5, 12, 7, 14, 18, 15, 31)	0.307 ± 0.3494	0.481 ± 1.9201	0.408 ± 1.5066	1.429 ± 3.1244	0.664 ± 1.6573	0.501 ± 1.2024	0.668 ± 1.8060
DU: Change at Day 28 (n=4, 2, 2, 4, 1, 4, 4)	0.598 ± 1.0962	0.196 ± 0.1767	0.536 ± 0.2524	0.221 ± 0.4645	1.071 ± 99999	1.011 ± 1.3398	0.446 ± 0.6262
Cl: Change at Day 1 (n=3,6,4,7,8,8,16)	4.000 ± 2.6458	0.167 ± 3.6560	-1.000 ± 1.4142	1.000 ± 2.5166	0.625 ± 1.6850	0.875 ± 3.3991	1.181 ± 2.6240
Cl: Change at Day 1 7h (n=2,8,3,6,7,8,16)	-0.500 ± 6.3640	0.125 ± 1.4577	-0.667 ± 7.3711	0.300 ± 3.0033	0.286 ± 3.1472	1.250 ± 3.4538	1.625 ± 2.5000
Cl: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 1)	99999 ± 99999	-4.000 ± 99999	0.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-3.000 ± 99999
Cl: Change at Day 4 (n=0, 1, 0, 0, 0, 1, 1)	99999 ± 99999	-3.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.000 ± 99999	4.000 ± 99999
Cl: Change at Day 5 (n=5, 13, 7, 14, 14, 15, 30)	3.000 ± 1.8708	-0.462 ± 2.8465	-1.000 ± 4.2426	0.871 ± 2.2293	0.143 ± 3.3936	0.667 ± 5.8269	0.617 ± 3.9950
Cl: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	4.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cl: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	8.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cl: Change at Day 11 (n=5, 12, 6, 14, 18, 15, 28)	3.600 ± 2.6077	0.500 ± 3.3166	1.167 ± 3.7103	1.079 ± 2.2723	0.500 ± 2.7279	0.467 ± 2.5317	1.471 ± 3.0841
Cl: Change at Day 28 (n=4, 2, 2, 2, 2, 4, 4)	3.750 ± 2.9861	-2.500 ± 0.7071	1.000 ± 1.4142	2.000 ± 2.8284	-1.000 ± 2.8284	2.000 ± 2.9439	1.000 ± 2.1602
BiC: Change at Day 1 (n=1,5,4,5,6,5,12)	-4.400 ± 99999	0.840 ± 2.0959	1.250 ± 1.3699	-3.220 ± 3.4347	-0.967 ± 4.0805	2.220 ± 2.2786	-0.100 ± 2.0596
BiC: Change at Day 1 7h (n=1,4,3,5,5,8,14)	1.600 ± 99999	0.200 ± 0.9092	0.667 ± 0.5774	1.240 ± 1.7126	1.600 ± 4.7518	0.425 ± 3.4446	0.100 ± 2.8914
BiC: Change at Day 3 (n=0,1,1,0,0,0,1)	99999 ± 99999	3.200 ± 99999	0.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.700 ± 99999
BiC: Change at Day 4 (n=0,1,0,0,0,0,0)	99999 ± 99999	1.500 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
BiC: Change at Day 5 (n=2,11,7,12,11,12,27)	-0.600 ± 2.9698	0.918 ± 2.3142	-0.457 ± 2.3853	-0.883 ± 4.6910	-1.045 ± 3.1986	-0.700 ± 1.8650	-1.674 ± 3.8609
BiC: Change at Day 11 (n=1,10,6,11,15,12,25)	-7.200 ± 99999	-1.470 ± 2.2696	-2.217 ± 2.9856	-0.282 ± 2.7239	-0.680 ± 3.3830	-1.342 ± 4.0514	-2.024 ± 3.3589
BiC: Change at Day 28 (n=1,1,2,2,1,2,3)	-0.100 ± 99999	-2.100 ± 99999	-6.850 ± 3.4648	0.950 ± 0.0707	-1.000 ± 99999	-2.000 ± 2.8284	-1.033 ± 4.0253
Glu: Change at Day 1 (n=3,5,5,9,8,8,16)	0.574 ± 0.1784	0.027 ± 0.3211	0.022 ± 1.0456	0.394 ± 0.9391	-1.131 ± 1.3339	0.118 ± 1.1405	-0.144 ± 1.0466
Glu: Change at Day 1 7h (n=2,8,3,7,8,8,16)	-0.944 ± 0.3140	0.524 ± 2.0440	0.444 ± 0.4441	-0.936 ± 1.8798	-0.180 ± 0.8312	-1.610 ± 1.7419	-0.200 ± 1.0311
Glu: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 1)	99999 ± 99999	4.774 ± 99999	-0.222 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-1.443 ± 99999
Glu: Change at Day 4 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	-2.220 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.389 ± 99999
Glu: Change at Day 5 (n=5, 13, 8, 16, 14, 15, 31)	-0.455 ± 1.1627	-0.589 ± 0.9103	0.056 ± 1.1074	-0.529 ± 1.4839	-1.321 ± 1.2549	-0.981 ± 1.1512	-0.597 ± 0.8138
Glu: Change at Day 11 (n=5, 12, 7, 15, 17, 15, 29)	-0.377 ± 0.7441	-0.735 ± 1.2051	-0.254 ± 0.7960	-0.540 ± 1.4190	-1.118 ± 1.2295	-0.855 ± 1.0013	-0.602 ± 0.8924
Glu: Change at Day 28 (n=3, 2, 2, 3, 1, 3, 3)	-0.259 ± 0.6941	-1.055 ± 1.0205	0.250 ± 0.5888	-0.403 ± 0.8107	-3.997 ± 99999	-2.368 ± 2.4198	-0.907 ± 0.3899
K: Change at Day 1 (n=3,6,5,8,8,8,16)	-0.367 ± 0.7371	-0.217 ± 0.5776	-0.100 ± 0.4743	0.446 ± 0.7071	0.663 ± 0.8667	-0.538 ± 0.4241	-0.158 ± 0.4367
K: Change at Day 1 7h (n=2,8,3,7,8,8,16)	0.000 ± 0.2828	-0.025 ± 0.6585	0.833 ± 0.8505	-0.35 ± 0.7678	0.163 ± 0.4138	0.166 ± 0.7890	-0.042 ± 0.4909
K: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 1)	99999 ± 99999	0.500 ± 99999	-0.100 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.400 ± 99999
K: Change at Day 4 (n=0, 1, 0, 0, 0, 1, 1)	99999 ± 99999	-0.300 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.400 ± 99999	0.100 ± 99999
K: Change at Day 5 (n=5, 14, 8, 16, 14, 15, 31)	-0.080 ± 0.5630	0.383 ± 0.4422	0.225 ± 0.7046	0.123 ± 0.7766	0.529 ± 0.4177	0.327 ± 0.6606	0.446 ± 0.7510
K: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.800 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
K: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-0.800 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
K: Change at Day 11 (n=5, 12, 7, 15, 18, 15, 30)	-0.180 ± 0.2683	0.367 ± 1.0008	0.386 ± 0.8214	0.019 ± 0.7057	0.328 ± 0.5154	0.207 ± 0.9098	0.296 ± 0.7519
K: Change at Day 28 (n=4, 2, 2, 4, 2, 4, 5)	-0.450 ± 0.3416	0.150 ± 0.9192	0.350 ± 0.4950	-0.200 ± 0.3367	0.650 ± 0.0707	0.250 ± 0.8583	0.000 ± 0.5148
Na: Change at Day 1 (n=3,6,5,8,8,8,17)	1.333 ± 3.2146	1.500 ± 1.6432	-0.600 ± 1.1402	-1.513 ± 3.3702	0.000 ± 1.8516	0.875 ± 2.2321	0.529 ± 2.7640
Na: Change at Day 1 7h (n=2,8,3,7,8,8,16)	-0.500 ± 6.3640	-0.250 ± 1.7525	-1.333 ± 4.9329	1.429 ± 4.1173	-0.250 ± 3.1510	1.000 ± 1.4142	0.188 ± 2.1360
Na: Change at Day 3 (n=0, 1, 1, 0, 0, 0, 1)	99999 ± 99999	-5.000 ± 99999	1.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-2.000 ± 99999
Na: Change at Day 4 (n=0, 1, 0, 0, 0, 1, 1)	99999 ± 99999	-4.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	1.000 ± 99999	0.000 ± 99999
Na: Change at Day 5 (n=5, 14, 8, 16, 14, 15, 32)	2.000 ± 2.7386	1.286 ± 2.2336	0.125 ± 3.6815	0.050 ± 3.6715	0.500 ± 3.1805	-1.400 ± 2.4437	0.344 ± 2.1192
Na: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	2.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Na: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	6.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Na: Change at Day 11 (n=5, 12, 7, 15, 18, 15, 29)	1.000 ± 2.8284	0.462 ± 1.8081	0.286 ± 4.1115	0.273 ± 2.6497	0.111 ± 2.6097	-0.867 ± 2.2318	-0.517 ± 2.2775
Na: Change at Day 28 (n=4, 2, 2, 4, 2, 4, 4)	1.500 ± 1.7321	-5.500 ± 0.7071	1.000 ± 0.0000	-0.667 ± 1.5275	0.500 ± 2.1213	-1.250 ± 2.0616	0.750 ± 2.8723

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Clinical laboratory Parameter (Hematology-Reticulocyte Absolute [RA], Platelets [Pl], Leukocytes [LU], Monocytes [MO], Neutrophils [NE])

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End point title

MAD: Change From Baseline in Clinical laboratory Parameter (Hematology-Reticulocyte Absolute [RA], Platelets [Pl], Leukocytes [LU], Monocytes [MO], Neutrophils [NE]) ^[55] ^[56]

End point description

Change from baseline in Hematology-RA, Pl, LU, MO, NE were assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline, Day 1, 5, 11 and Day 28

Notes
[55] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: 10^9/L
arithmetic mean (standard deviation)
RA: Change at Day 1 (n=0,1,1,3,0,0,2)	99999 ± 99999	12.300 ± 99999	0.700 ± 99999	-1.867 ± 7.7861	99999 ± 99999	99999 ± 99999	-7.750 ± 13.3643
RA: Change at Day 1 7h (n=0,1,0,1,1,1,2)	99999 ± 99999	-16.000 ± 99999	99999 ± 99999	174.000 ± 99999	16.000 ± 99999	4.000 ± 99999	1.500 ± 2.1213
RA: Change at Day 5 (n=0,2,1,4,2,0,6)	99999 ± 99999	22.600 ± 4.8083	25.000 ± 99999	21.433 ± 23.1768	20.000 ± 99999	99999 ± 99999	19.050 ± 38.6507
RA: Change at Day 11 (n=0, 2, 1, 4, 2, 0, 6)	99999 ± 99999	29.100 ± 28.1428	20.100 ± 99999	33.550 ± 32.7856	15.050 ± 1.3435	99999 ± 99999	74.250 ± 75.8861
RA: Change at Day 28 (n=0, 0, 0, 2, 1, 0, 2)	99999 ± 99999	99999 ± 99999	99999 ± 99999	-7.400 ± 10.4652	-1.700 ± 99999	99999 ± 99999	11.950 ± 11.2430
Pl: Change at Day 1 (n=3,6,5,7,8,7,16)	55.333 ± 139.2204	-69.833 ± 127.8928	15.000 ± 36.4211	30.143 ± 49.7475	21.125 ± 38.0768	13.286 ± 102.5032	-9.375 ± 83.1199
Pl: Change at Day 1 7h (n=2,8,3,7,8,8,15)	102.000 ± 45.2548	-26.125 ± 79.3013	2.333 ± 65.2482	14.429 ± 118.0408	1.625 ± 51.1411	28.000 ± 49.7106	30.200 ± 96.7207
Pl: Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	14.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	220.000 ± 99999
Pl: Change at Day 4 (n=0, 1, 0, 1, 1, 1, 1)	99999 ± 99999	-4.000 ± 99999	99999 ± 99999	187.000 ± 99999	25.000 ± 99999	8.000 ± 99999	266.000 ± 99999
Pl: Change at Day 5 (n=5, 13, 7, 16, 14, 14, 30)	176.200 ± 147.7031	85.538 ± 80.9852	116.571 ± 77.5411	126.000 ± 173.6241	51.429 ± 127.6279	93.214 ± 105.2866	148.467 ± 131.1471
Pl: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	33.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Pl: Change at Day 7 (n=1, 0, 0, 0, 0, 0)	246.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Pl: Change at Day 11 (n=5, 14, 7, 16, 18, 14, 30)	224.400 ± 187.1692	184.143 ± 161.7576	146.000 ± 139.5087	161.563 ± 143.9111	97.056 ± 135.6741	62.857 ± 152.4996	189.067 ± 199.0547
Pl: Change at Day 28 (n=4, 2, 3, 4, 7, 5, 5)	-1.250 ± 77.3235	53.500 ± 187.3833	51.667 ± 46.1988	90.250 ± 114.7123	64.857 ± 80.6090	90.000 ± 82.5530	105.200 ± 93.8840
LU: Change at Day 1 (n=3,6,5,8,8,8,16)	-0.947 ± 4.2824	-0.458 ± 4.6275	1.496 ± 1.5027	2.224 ± 5.2023	-0.109 ± 1.8526	-1.759 ± 2.4622	-0.646 ± 2.8928
LU: Change at Day 1 7h (n=2,8,3,7,8,8,16)	4.105 ± 1.5344	-0.026 ± 2.2113	1.830 ± 4.4559	0.779 ± 3.0700	1.449 ± 5.0896	1.004 ± 3.1465	0.737 ± 2.9601
LU: Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	3.700 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	3.500 ± 99999
LU: Change at Day 4 (n=0, 1, 0, 1, 1, 1, 1)	99999 ± 99999	2.600 ± 99999	99999 ± 99999	2.900 ± 99999	1.800 ± 99999	-2.410 ± 99999	10.600 ± 99999
LU: Change at Day 5 (n=5, 14, 7, 16, 14, 15, 30)	4.658 ± 4.0670	2.899 ± 4.1105	2.617 ± 2.8576	1.919 ± 4.1434	1.018 ± 3.5099	-1.158 ± 4.8667	2.047 ± 3.6648
LU: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	1.700 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
LU: Change at Day 7 (n=1, 0, 0, 0, 0, 0)	-5.200 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
LU: Change at Day 11 (n=5, 14, 7, 16, 18, 15, 30)	2.202 ± 4.2067	1.343 ± 3.4003	1.560 ± 6.3322	1.051 ± 3.7508	0.966 ± 3.1490	-1.252 ± 5.3719	1.596 ± 3.9254
LU: Change at Day 28 (n=4, 2, 3, 4, 7, 5, 5)	0.990 ± 3.8787	2.350 ± 5.4447	2.340 ± 3.7843	1.305 ± 5.8319	2.131 ± 2.2922	-0.232 ± 1.2545	1.734 ± 2.8677
MO: Change at Day 1 (n=0,2,5,6,7,4,8)	99999 ± 99999	0.5400 ± 1.47078	0.4060 ± 0.77797	0.1517 ± 1.29711	-0.1277 ± 0.37158	-0.4441 ± 0.59779	-0.3081 ± 0.96999
MO: Change at Day 1 7h (n=2,3,3,5,5,6,10)	0.3300 ± 0.12728	-0.4700 ± 0.68088	-0.8033 ± 1.62254	0.4122 ± 0.71410	0.2389 ± 0.43763	-0.2541 ± 0.35293	-0.3696 ± 0.74369
MO: Change at Day 4 (n=0, 0, 0, 1, 0, 1, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.3000 ± 99999	99999 ± 99999	-0.6900 ± 99999	99999 ± 99999
MO: Change at Day 5 (n=2, 6, 7, 12, 10, 9, 18)	-0.0850 ± 0.19092	0.3633 ± 0.82553	-0.5700 ± 1.47410	-0.0713 ± 0.59409	-0.3018 ± 0.45398	-0.9631 ± 0.78187	-0.2382 ± 0.73679
MO: Change at Day 11 (n=2, 6, 7, 1`2, 14, 9, 19)	-0.2300 ± 0.25456	-0.6133 ± 0.23763	-0.5600 ± 1.40801	-0.3043 ± 0.98092	-0.2959 ± 0.52460	-0.7158 ± 0.80561	-0.5811 ± 0.74793
MO: Change at Day 28 (n=2, 0, 3, 2, 6, 4, 1)	-0.2800 ± 0.31113	99999 ± 99999	0.0700 ± 0.72794	-0.1850 ± 0.54447	0.2202 ± 0.61356	-0.5366 ± 0.47212	0.0000 ± 99999
NE: Change at Day 1 (n=0,3,5,6,7,4,8)	99999 ± 99999	-0.1500 ± 2.11714	-0.1040 ± 0.94664	-0.1117 ± 2.67649	-1.1420 ± 1.36427	-1.3210 ± 1.38441	-1.7673 ± 2.27238
NE: Change at Day 1 7h (n=2,5,3,5,5,6,11)	-0.3000 ± 0.42426	-0.7100 ± 2.05825	0.7323 ± 0.81159	0.0688 ± 1.92003	-0.2506 ± 0.94318	-0.4207 ± 1.81599	-0.0937 ± 1.63375
NE: Change at Day 4 (n=0, 0, 0, 1, 0, 1, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	5.3000 ± 99999	99999 ± 99999	-1.4800 ± 99999	99999 ± 99999
NE: Change at Day 5 (n=2, 8, 7, 12, 14, 9, 19)	0.1800 ± 1.32936	-0.6150 ± 1.99115	0.7381 ± 1.94822	0.6671 ± 2.26738	-0.9553 ± 1.06988	-2.1604 ± 4.01227	-0.5921 ± 2.92195
NE: Change at Day 11 (n=2, 8, 7, 12, 14, 9, 19)	0.2200 ± 1.15966	-0.6350 ± 2.62318	-0.2574 ± 1.89726	-0.1292 ± 2.35877	-1.0729 ± 1.47713	-2.8000 ± 3.77919	-0.7321 ± 3.54809
NE: Change at Day 28 (n=2, 0, 3, 2, 6, 4, 1)	-0.7350 ± 0.36062	99999 ± 99999	0.8800 ± 0.45133	2.5500 ± 4.73762	-0.6352 ± 0.67595	-2.3981 ± 1.49300	-0.7000 ± 99999

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Reticulocyte Percent, Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, and Lymphocytes/Leukocytes

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End point title

MAD: Change From Baseline in Reticulocyte Percent, Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, and Lymphocytes/Leukocytes ^[57] ^[58]

End point description

Change from baseline in Hematology- RE, HeT, B/LU, E/LU, Ly/LU, N/LU and MO/LU were assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. in respective arm. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline, Day 1, 3, 4, 5, 11 and Day 28

Notes
[57] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: Fraction of 1
arithmetic mean (standard deviation)
RE: Change at Day 1 (n=3,3,3,3,6,8,12)	-0.00100 ± 0.001000	-0.00033 ± 0.000577	0.00210 ± 0.002152	0.00033 ± 0.002517	0.00052 ± 0.001443	-0.00114 ± 0.003794	0.00038 ± 0.002702
RE:Change at Day 1 7h (n=2,5,2,6,5,7,11)	0.00255 ± 0.006293	-0.00364 ± 0.004219	0.00140 ± 0.003394	0.00330 ± 0.006239	-0.00110 ± 0.00258	0.00010 ± 0.00296	0.00499 ± 0.011443
RE:Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.03000 ± 99999
RE:Change at Day 4 (n=0, 1, 0, 0, 1, 0, 1)	99999 ± 99999	0.00100 ± 99999	99999 ± 99999	99999 ± 99999	-0.00200 ± 99999	99999 ± 99999	0.01000 ± 99999
RE:Change at Day 5 (n=5, 8, 4, 9, 11, 15, 21	0.00650 ± 0.002373	0.00093 ± 0.007055	0.00020 ± 0.002903	0.00253 ± 0.006009	-0.00118 ± 0.003986	-0.00591 ± 0.006861	0.00515 ± 0.008977
RE:Change at Day 7 (n=1, 0, 0, 0, 0, 0)	0.01220 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
RE: Change at Day 11 (n=5, 8, 5, 9, 13, 15, 21)	0.00458 ± 0.007345	0.00671 ± 0.007802	0.01088 ± 0.005876	0.00759 ± 0.012458	0.00936 ± 0.008564	0.01654 ± 0.028015	0.00694 ± 0.005788
RE:Change at Day 28 (n=4, 2, 1, 1, 3 ,5, 2)	-0.00045 ± 0.007967	0.00310 ± 0.015415	-0.00200 ± 99999	0.00200 ± 99999	0.00480 ± 0.006702	0.00484 ± 0.005498	0.00300 ± 0
HeT:Change at Day 1 (n=3,6,5,8,8,8,15)	-0.0103 ± 0.04636	-0.0067 ± 0.02911	0.0002 ± 0.01472	0.0021 ± 0.01802	-0.0026 ± 0.01160	-0.0330 ± 0.02734	-0.0084 ± 0.02084
HeT:Change at Day 1 7h (n=2,8,3,7,8,8,16)	0.0145 ± 0.02616	-0.0162 ± 0.03420	-0.0127 ± 0.02969	-0.0170 ± 0.03645	-0.0009 ± 0.02047	-0.0006 ± 0.01862	-0.0104 ± 0.02869
HeT:Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	-0.0500 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.0010 ± 99999
HeT:Change at Day 4 (n=0, 1, 0, 1, 1, 1, 1)	99999 ± 99999	-0.0830 ± 99999	99999 ± 99999	-0.0460 ± 99999	0.0210 ± 99999	-0.0060 ± 99999	0.0240 ± 99999
HeT: Change at Day 5 (n=5, 14, 7, 16, 14, 15, 29)	0.0114 ± 0.03206	0.0052 ± 0.03671	0.0213 ± 0.02721	-0.0049 ± 0.04071	0.0036 ± 0.02690	-0.0070 ± 0.03210	0.0019 ± 0.02624
HeT:Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.0280 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
HeT:Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-0.0380 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
HeT:Change at Day 11 (n=5, 14, 7, 16, 18, 15, 29)	0.0104 ± 0.03093	-0.0006 ± 0.03947	0.0130 ± 0.05371	-0.0021 ± 0.03684	-0.0080 ± 0.02276	-0.0247 ± 0.02871	-0.0020 ± 0.02726
HeT:Change at Day 28 (n=4, 2, 3, 4, 7, 5, 4)	0.0255 ± 0.02947	-0.0585 ± 0.11384	0.0563 ± 0.04649	0.0233 ± 0.04339	0.0279 ± 0.03936	0.0008 ± 0.01829	0.0080 ± 0.03429
B/LU:Change at Day 1 (n=3,6,4,6,8,7,12)	-0.0007 ± 0.00115	-0.0005 ± 0.00071	0 ± 0.00316	0.0030 ± 0.00548	-0.0038 ± 0.00787	0.0021 ± 0.00353	-0.0001 ± 0.00360
B/LU:Change at Day 1 7h (n=2,4,3,7,7,6,12)	0.0020 ± 0.00424	-0.0018 ± 0.00556	-0.0040 ± 0.00600	0 ± 0	-0.0003 ± 0.01098	-0.0012 ± 0.00440	0.0006 ± 0.00491
B/LU:Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.0040 ± 99999
B/LU:Change at Day 4 (n=0, 1, 0, 1, 1, 1, 1)	99999 ± 99999	0 ± 99999	99999 ± 99999	-0.0030 ± 99999	0.0050 ± 99999	0.0020 ± 99999	0 ± 99999
B/LU:Change at Day 5 (n=5, 7, 6, 14, 13, 13, 22)	-0.0002 ± 0.00179	-0.0029 ± 0.00426	-0.0033 ± 0.00333	0.0011 ± 0.00388	-0.0001 ± 0.00971	-0.0002 ± 0.00424	0.0010 ± 0.00501
B/LU:Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.0020 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
B/LU:Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	0.0100 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
B/LU:Change at Day 11 (n=5, 7, 5, 13, 16, 13, 22)	0.0004 ± 0.00297	-0.0003 ± 0.00585	-0.0032 ± 0.00349	0.0026 ± 0.00441	-0.0024 ± 0.00896	-0.0007 ± 0.00563	-0.0003 ± 0.00372
B/LU:Change at Day 28 (n=4, 2, 3, 3, 6, 5, 4)	-0.0005 ± 0.00129	0 ± 0.01414	-0.0010 ± 0.00100	0.0033 ± 0.00577	-0.0023 ± 0.00622	-0.0012 ± 0.00507	0.0025 ± 0.00574
E/LU:Change at Day 1 (n=3,3,4,6,8,7,12)	0.0170 ± 0.01480	-0.0140 ± 0.01400	0.0108 ± 0.01190	-0.0033 ± 0.02069	0.0139 ± 0.00919	0.0016 ± 0.00969	0.0027 ± 0.01069
E/LU:Change at Day 1 7h (n=22,5,2,7,7,6,11)	0.0040 ± 0.00424	0.0130 ± 0.03655	0.0150 ± 0.00849	-0.0064 ± 0.01796	0.0027 ± 0.00663	0.0110 ± 0.01515	0.0135 ± 0.02070
E/LU:Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	0.0300 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.0160 ± 99999
E/LU:Change at Day 4 (n=0, 1, 0, 1, 1, 1, 1)	99999 ± 99999	0.0600 ± 99999	99999 ± 99999	-0.0080 ± 99999	0.0220 ± 99999	0.0020 ± 99999	0.0100 ± 99999
E/LU:Change at Day 5 (n=5, 8, 5 ,14, 13, 13, 21)	0.0218 ± 0.01388	0.0050 ± 0.01996	0.0220 ± 0.01190	0.0047 ± 0.01722	0.0226 ± 0.01823	0.0130 ± 0.01194	0.0219 ± 0.02104
E/LU:Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.0210 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
E/LU:Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	0.0600 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
E/LU:Change at Day 11 (n=5, 7, 5, 13, 16, 13, 22)	0.0210 ± 0.01725	0.0019 ± 0.02660	0.0124 ± 0.00814	0.0057 ± 0.02356	0.0226 ± 0.01821	0.0048 ± 0.00826	0.0125 ± 0.01627
E/LU:Change at Day 28 (n=4, 2, 3, 3, 6, 5, 4)	0.0393 ± 0.02254	0 ± 0.01414	0.0400 ± 0.00265	0.0263 ± 0.01518	0.0313 ± 0.01715	0.0334 ± 0.02924	0.0248 ± 0.03362
Ly/LU:Change at Day 1 (n=3,3,4,6,8,7,12)	0.0647 ± 0.15279	0.0053 ± 0.06795	0.0313 ± 0.12570	0.1023 ± 0.11833	0.1145 ± 0.13475	0.0309 ± 0.12500	0.0216 ± 0.13094
Ly/LU:Change at Day 1 7h (n=2,6,3,7,7,6,12)	0.1900 ± 0.05091	0.1003 ± 0.11078	0.0043 ± 0.03550	0.0114 ± 0.13422	0.1856 ± 0.10153	0.1557 ± 0.13484	0.1263 ± 0.15505
Ly/LU:Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	-0.1000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.2770 ± 99999
Ly/LU:Change at Day 4 (n=0, 1, 0, 1, 1, 1, 1)	99999 ± 99999	-0.1400 ± 99999	99999 ± 99999	-0.4180 ± 99999	0.3010 ± 99999	0.0590 ± 99999	0.0500 ± 99999
Ly/LU:Change at Day 5 (n=5, 9, 6, 14, 13, 13, 22)	0.0436 ± 0.16829	0.0973 ± 0.14759	-0.0207 ± 0.06181	0.0243 ± 0.14084	0.2381 ± 0.13613	0.1698 ± 0.17056	0.0719 ± 0.13371
Ly/LU:Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.1740 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Ly/LU:Change at Day 7 (n=1,0,0,0,0,0,0)	0.1700 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Ly/LU:Change at Day 11(n=5,9,6,13,16,13,22)	0.0802 ± 0.13331	0.0914 ± 0.15882	0.1217 ± 0.13303	0.0528 ± 0.18947	0.1951 ± 0.17741	0.2074 ± 0.17816	0.0785 ± 0.15841
Ly/LU:Change at Day 28(n=4,2,3,3,6,5,4)	0.1740 ± 0.18472	0.1850 ± 0.00707	-0.0527 ± 0.05065	-0.1037 ± 0.19995	0.1642 ± 0.16080	0.2072 ± 0.20963	0.1443 ± 0.03622
NE/LU:Change at Day 1(n=3,3,4,6,8,7,12)	-0.0487 ± 0.14075	-0.0217 ± 0.03731	-0.0315 ± 0.12331	-0.0817 ± 0.15243	-0.1073 ± 0.12579	-0.0257 ± 0.13069	-0.3081 ± 0.96999
NE/LU:Change at Day 1 7h (n=2,6,3,7,7,6,12)	-0.1835 ± 0.03323	-0.1087 ± 0.07159	0.0167 ± 0.00666	-0.0107 ± 0.17936	-0.1730 ± 0.08578	-0.1290 ± 0.13407	-0.0077 ± 0.13576
NE/LU:Change at Day 3(n=0,1,0,0, 0,0,1)	99999 ± 99999	0.0500 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.1172 ± 0.12884
NE/LU:Change at Day 4(n=0,1,0,1, 1,1,1)	99999 ± 99999	0.0700 ± 99999	99999 ± 99999	0.4260 ± 99999	-0.3010 ± 99999	-0.0350 ± 99999	-0.0600 ± 99999
NE/LU:Change at Day 5(n=5,9,6,14, 13,13,22)	-0.0304 ± 0.15891	-0.0728 ± 0.13749	0.0617 ± 0.06439	0.0050 ± 0.15536	-0.2025 ± 0.12148	-0.1022 ± 0.16801	-0.0815 ± 99999
NE/LU: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.1590 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
NE/LU:Change at Day 7(n=1,0,0,0, 0,0,0)	-0.2000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
N/L:Change at Day 11(n=5,9,6,13,16,13,22)	-0.0432 ± 0.12650	-0.0607 ± 0.14905	-0.0408 ± 0.11622	-0.0230 ± 0.21813	-0.1760 ± 0.15354	-0.1668 ± 0.18456	-0.0465 ± 0.16944
NE/LU:Change at Day 28(n=4,2,3,3,6,5,4)	-0.1605 ± 0.13847	-0.1300 ± 0	0.0447 ± 0.02442	0.1287 ± 0.20146	-0.1763 ± 0.08492	-0.1830 ± 0.24943	-0.1225 ± 0.08685
MO/LU:Change at Day 1(n=3,3,4,6,8,7,12)	-0.0257 ± 0.03707	0.0273 ± 0.03855	-0.0115 ± 0.00645	-0.0223 ± 0.06961	-0.0057 ± 0.03163	-0.0201 ± 0.02559	-0.0148 ± 0.05153
MO/LU:Change at Day 1, 7h(n= 2, 6, 3, 7, 7, 6, 12)	-0.0125 ± 0.01768	-0.0018 ± 0.04649	-0.0797 ± 0.11327	0 ± 0.05292	-0.0176 ± 0.03777	-0.0277 ± 0.01461	-0.0215 ± 0.05408
MO/LU: Change at Day 3 (n=0, 1, 0, 0 ,0, 0, 1)	99999 ± 99999	0.0200 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.0190 ± 99999
MO/LU: Change at Day 4 (n=0, 1, 0, 1, 1, 1, 1)	99999 ± 99999	-0.0200 ± 99999	99999 ± 99999	-0.0010 ± 99999	-0.0170 ± 99999	-0.0280 ± 99999	-0.0100 ± 99999
MO/LU: Change at Day 5 (n=5, 9, 6 ,14, 13, 13, 22)	-0.0348 ± 0.01645	-0.0296 ± 0.03387	-0.0953 ± 0.08841	-0.0347 ± 0.04417	-0.0448 ± 0.04020	-0.0763 ± 0.03677	-0.0287 ± 0.04721
MO/LU: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.0380 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
MO/LU: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-0.0300 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
MO/LU: Change at Day 11 (n=5,9, 6,13,16,13,22)	-0.0524 ± 0.03692	-0.0353 ± 0.04317	-0.0870 ± 0.06773	-0.0299 ± 0.05849	-0.0236 ± 0.04057	-0.0448 ± 0.03341	-0.0405 ± 0.03295
MO/LU: Change at Day 28 (n=4, 2, 2, 3, 6, 5, 4)	-0.0448 ± 0.03924	-0.050 ± 0.02828	-0.0445 ± 0.04313	-0.0547 ± 0.02335	0.0110 ± 0.03289	-0.0546 ± 0.03049	-0.0415 ± 0.04273

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin)

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End point title

MAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin) ^[59] ^[60]

End point description

Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin) was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline, Day 1, 3, 4, 5, 6, 7, 11 and Day 28

Notes
[59] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: pg
arithmetic mean (standard deviation)
Change at Day 1 (n=3, 6, 5, 8, 8, 8, 8, 16)	-0.033 ± 0.7572	-0.467 ± 0.4719	-0.020 ± 0.5119	0.587 ± 1.0921	-0.162 ± 0.3249	0.062 ± 0.8400	-0.050 ± 0.5279
Change at Day 1 7h (n=2, 8, 3, 7, 8, 8, 16)	-0.200 ± 0.8485	0.100 ± 0.4957	0.167 ± 0.4619	-0.600 ± 0.7234	0.225 ± 0.5175	-0.112 ± 0.4190	-0.175 ± 1.1072
Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	-0.500 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.400 ± 99999
Change at Day 4 (n=0, 1, 0, 1, 1, 1, 1)	99999 ± 99999	-0.200 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.100 ± 99999
Change at Day 5 (n=5, 14, 7, 16, 14, 15, 30)	-0.300 ± 0.4472	-0.236 ± 0.5624	-0.371 ± 0.5376	0.250 ± 1.7084	0.000 ± 0.7565	0.087 ± 0.9180	-0.173 ± 0.8068
Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.500 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-0.500 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Change at Day 11 (n=5, 14, 7, 16, 18, 15, 30)	-0.460 ± 0.8142	-0.443 ± 0.5019	-0.129 ± 0.5936	-0.138 ± 1.2010	-0.111 ± 0.6970	0.073 ± 1.0229	-0.533 ± 0.5868
Change at Day 28 (n=4, 2, 3, 4, 7, 5, 5)	-0.050 ± 0.6807	-1.800 ± 0.2828	-1.133 ± 1.6166	-0.550 ± 1.1958	0.343 ± 0.9235	0.320 ± 3.0425	-1.180 ± 1.4025

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular HGB Concentration)

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End point title

MAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular HGB Concentration) ^[61] ^[62]

End point description

Change from baseline in clinical laboratory parameter (Hematology- erythrocytes mean corpuscular HGB concentration) was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline to Day 1, 3, 4, 5, 6, 7, 11 and Day 28

Notes
[61] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: g/L
arithmetic mean (standard deviation)
Change at Day 1 (n=3, 6, 5, 8, 8, 8, 8, 16)	-0.667 ± 6.6583	0.000 ± 4.5607	-3.600 ± 6.1887	0.500 ± 8.1670	-0.375 ± 6.6103	-1.500 ± 11.0454	-1.750 ± 6.8069
Change at Day 1 7h (n=2, 8, 3, 7, 8, 8, 16)	1.000 ± 11.3137	2.875 ± 4.6733	5.333 ± 10.0167	-6.714 ± 6.3957	2.429 ± 9.2711	-0.375 ± 9.1486	-0.063 ± 14.5349
Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	-2.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	1.000 ± 99999
Change at Day 4 (n=0, 1, 0, 1, 1, 1, 1)	99999 ± 99999	1.000 ± 99999	99999 ± 99999	10.000 ± 99999	12.000 ± 99999	-6.000 ± 99999	-1.000 ± 99999
Change at Day 5 (n=5, 14, 7, 14, 13, 15, 30)	1.600 ± 8.0187	2.000 ± 6.8388	0.857 ± 4.4508	0.857 ± 11.4518	5.154 ± 14.3169	4.333 ± 9.6115	3.233 ± 9.8250
Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	-2.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-3.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Change at Day 11 (n=5, 14, 7, 14, 17, 15, 30)	-1.000 ± 8.6891	3.143 ± 9.3138	-2.571 ± 8.1416	-1.000 ± 10.2582	2.176 ± 8.8898	7.400 ± 13.5320	1.800 ± 8.2144
Change at Day 28 (n=4, 2, 3, 3, 7, 5, 5)	6.750 ± 6.2383	-8.500 ± 13.4350	4.667 ± 8.5049	2.000 ± 7.0000	0.714 ± 14.9634	-4.600 ± 18.2975	-1.000 ± 7.8740

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Erythrocytes Mean Corpuscular Volume [e-MCV] and Mean Platelet Volume [MPV])

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End point title

MAD: Change From Baseline in Clinical Laboratory Parameter (Erythrocytes Mean Corpuscular Volume [e-MCV] and Mean Platelet Volume [MPV]) ^[63] ^[64]

End point description

Change from Baseline in Clinical Laboratory Parameter (e-MCV and MPV) was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline, Day 1, 3, 4, 5, 6, 7, 11 and Day 28

Notes
[63] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: FL
arithmetic mean (standard deviation)
e-MCV: Change at Day 1 (n=3,6,5,8,8,8,16)	0.167 ± 0.7234	-1.300 ± 0.8649	0.760 ± 0.9940	1.325 ± 5.1917	-0.213 ± 1.1344	0.188 ± 1.0480	0.237 ± 1.7258
e-MCV: Change at Day 1 7h (n=2, 8, 3, 7, 8, 8, 16)	-0.850 ± 0.4950	-0.500 ± 1.3690	-1.033 ± 1.8502	0.043 ± 1.4954	-0.225 ± 1.8584	-0.412 ± 1.2287	-0.375 ± 2.6532
e-MCV: Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	-0.700 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	-1.700 ± 99999
e-MCV: Change at Day 4 (n=0, 1, 0, 1, 1, 1, 1)	99999 ± 99999	-0.700 ± 99999	99999 ± 99999	-0.100 ± 99999	-0.600 ± 99999	0.200 ± 99999	0.400 ± 99999
e-MCV:Change at Day 5(n=5, 13, 7, 16, 14, 15, 30)	-1.320 ± 1.6022	-1.177 ± 1.5034	-1.429 ± 1.0095	0.281 ± 3.4582	-1.236 ± 2.9014	-1.107 ± 1.5121	-1.240 ± 2.0346
e-MCV: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	-1.300 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
e-MCV: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-0.900 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
e-MCV: Change at Day 11 (n=5,13,7,16,18,15,30)	-1.140 ± 1.7925	-2.138 ± 1.9410	0.386 ± 2.1567	0.017 ± 3.7913	-0.861 ± 2.3722	-1.980 ± 2.3373	-2.053 ± 2.1800
e-MCV: Change at Day 28 (n=4, 2, 3, 4, 7, 5, 5)	-1.775 ± 2.0549	-3.050 ± 4.4548	-4.533 ± 2.9738	-1.925 ± 2.3543	0.571 ± 3.3678	0.820 ± 4.7457	-3.180 ± 3.1364
MPV: Change at Day 1 (n=3,4,5,8,7,13)	-0.400 ± 0.6557	0.050 ± 0.3697	0.200 ± 0.3391	1.220 ± 1.2317	-0.075 ± 0.5175	0.286 ± 0.8375	0.069 ± 0.5105
MPV: Change at Day 1 7h (n=2, 7, 2, 6, 7, 8, 12)	0.250 ± 0.2121	0.171 ± 0.4071	-0.050 ± 0.6364	-0.233 ± 0.5750	-0.029 ± 0.3302	-0.075 ± 0.9051	0.183 ± 0.9272
MPV: Change at Day 4 (n=0, 0, 0, 0, 1, 1, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.100 ± 99999	0.000 ± 99999	99999 ± 99999
MPV: Change at Day 5 (n=5, 10, 6, 11, 13, 14, 24)	0.220 ± 0.1643	-0.200 ± 0.3830	-0.100 ± 0.2828	0.045 ± 0.7815	0.115 ± 0.7777	0.350 ± 0.8707	0.021 ± 0.5517
MPV: Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	-0.200 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
MPV: Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-0.100 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
MPV: Change at Day 11 (n=5,11,6,11,16,14,23)	-0.460 ± 0.8019	-0.091 ± 0.6236	0.383 ± 0.5193	0.282 ± 0.7795	0.038 ± 0.4064	0.507 ± 0.7405	-0.087 ± 0.5480
MPV: Change at Day 28 (n=4, 1, 3, 1, 6, 3, 2)	0.025 ± 0.2986	-0.200 ± 99999	0.267 ± 0.4041	0.800 ± 99999	-0.017 ± 0.8280	-0.367 ± 0.8327	0.050 ± 0.2121

No statistical analyses for this end point

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Erythrocytes Distribution Width)

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End point title

MAD: Change From Baseline in Clinical Laboratory Parameter (Erythrocytes Distribution Width) ^[65] ^[66]

End point description

Change From Baseline in Hematology-Erythrocytes Distribution Width was assessed. Safety analysis set defined as all randomized subjects who received at least 1 dose of study medication. Here "99999" indicates data was not evaluated at specified timepoint. Here "n" indicates number of subjects evaluated at specific timepoints.

End point type

Primary

End point timeframe

From Baseline to Day 1, 3, 4, 5, 6, 7, 11 and Day 28

Notes
[65] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
[66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	14	8	17	18	16	33
Units: Percentage (%)
arithmetic mean (standard deviation)
Change at Day 1 (n=3,4,5,5,8,8,13)	-0.133 ± 0.4726	-0.025 ± 0.0500	-0.100 ± 0.2550	-0.020 ± 0.2775	-0.150 ± 0.2449	0.138 ± 0.4719	0.131 ± 0.4461
Change at Day 1 7h (n=2, 8, 3, 7, 7, 8, 15)	-0.100 ± 0.2828	-0.087 ± 0.3091	-0.033 ± 0.1528	0.043 ± 0.3735	0.014 ± 0.2795	0.162 ± 0.4069	0.173 ± 0.3990
Change at Day 3 (n=0, 1, 0, 0, 0, 0, 1)	99999 ± 99999	0.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.400 ± 99999
Change at Day 4 (n=0, 1, 0, 1, 1, 1, 0)	99999 ± 99999	0.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Change at Day 5 (n=5, 12, 7, 13, 13, 15, 27)	-0.160 ± 0.5413	-0.083 ± 0.3271	3.271 ± 8.7007	0.031 ± 0.3987	-0.108 ± 0.4699	-0.213 ± 0.5222	0.081 ± 0.4715
Change at Day 6 (n=0, 0, 0, 1, 0, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.100 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Change at Day 7 (n=1, 0, 0, 0, 0, 0, 0)	-1.000 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Change at Day 11 (n=5,12,7,13,16,15,26)	0.280 ± 0.4324	0.350 ± 0.5351	1.286 ± 0.5273	0.646 ± 0.7655	0.406 ± 1.7883	0.007 ± 1.1068	0.281 ± 0.4373
Change at Day 28 (n=4, 2, 3, 2, 6, 5, 3)	0.150 ± 0.3697	-0.900 ± 1.2728	0.533 ± 0.9609	1.400 ± 0.9899	2.883 ± 1.0797	3.620 ± 1.9690	0.500 ± 0.5292

No statistical analyses for this end point

Secondary: SAD: Respiratory Syncytial Virus (RSV) viral Ribonucleic Acid (RNA) Concentrations in Nasal Swabs or Aspirates - FAS Infected: Virology Set

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End point title

SAD: Respiratory Syncytial Virus (RSV) viral Ribonucleic Acid (RNA) Concentrations in Nasal Swabs or Aspirates - FAS Infected: Virology Set ^[67]

End point description

RSV viral RNA concentration in nasal swabs or aspirates was assessed by quantitative RT-PCR in Log 10 Plaque forming units per mililitre (PFUe/mL). The Full Analysis Set–Infected Virology (FAS-IV) population is defined to include all FAS-I subjects who have sufficient virology data for analysis. Subjects were considered not have sufficient virology data for analysis and will be removed from the FAS-IV population if any of the conditions were met-baseline viral load is less then (<) 2 log10 PFUe/mL; missing baseline viral load; percent of intended volume administered is < 50% for the loading dose or total maintenance dose or < 3 viral load observations during the first 120 hours. Here, 'n' signifies the number of subjects analyzed at specified time point. Here "99999" indicates data was not evaluated at specified timepoint.

End point type

Secondary

End point timeframe

Baseline to Day 7

Notes
[67] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	Placebo
Number of subjects analysed	15	17	14	3	16
Units: Log 10 PFUe/mL
arithmetic mean (standard deviation)
Baseline (n=15, 17, 14, 3, 16)	4.933 ± 1.3126	5.567 ± 1.3314	6.188 ± 0.7897	4.700 ± 1.3604	5.123 ± 1.6435
Day 1 (n=13, 17, 14, 3, 16)	4.417 ± 1.8042	5.170 ± 1.4124	5.875 ± 1.4416	4.667 ± 0.4924	5.114 ± 1.6727
Day 2 (n=14, 14, 13, 3, 15)	4.154 ± 1.8270	4.503 ± 1.2868	5.376 ± 1.2581	4.477 ± 0.4879	4.531 ± 2.2140
Day 3 (n=2, 2, 2, 0, 0)	4.785 ± 1.3364	5.338 ± 2.6269	5.625 ± 0.2192	99999 ± 99999	99999 ± 99999
Day 4 (n=1, 0, 2, 0, 0)	4.940 ± 99999	99999 ± 99999	6.055 ± 1.1526	99999 ± 99999	99999 ± 99999
Day 5 (n=0, 0, 2, 0, 0)	99999 ± 99999	99999 ± 99999	4.665 ± 0.1344	99999 ± 99999	99999 ± 99999
Day 6 (n=0, 0, 1, 0, 0)	99999 ± 99999	99999 ± 99999	4.890 ± 99999	99999 ± 99999	99999 ± 99999
day 7 (n=14, 15, 12, 2, 15)	2.189 ± 1.4523	2.469 ± 1.5193	3.808 ± 1.5745	2.756 ± 2.2688	2.751 ± 1.9724

No statistical analyses for this end point

Secondary: SAD: RSV viral RNA Concentrations in Nasal Swabs or Aspirates - FAS: Infected

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End point title

SAD: RSV viral RNA Concentrations in Nasal Swabs or Aspirates - FAS: Infected ^[68]

End point description

RSV viral RNA concentrations in nasal swabs or aspirates was assessed by quantitative RT-PCR. The Full Analysis Set–Infected (FAS-I) is defined to include all FAS subjects who were confirmed PCR positive for RSV viral RNA. Here, 'n' signifies the number of subjects analyzed at specified time point. Here "99999" indicates data was not evaluated at specified timepoint.

End point type

Secondary

End point timeframe

Baseline to Day 7

Notes
[68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)	SAD: Placebo
Number of subjects analysed	18	17	14	3	17
Units: log10 PFUe/mL
arithmetic mean (standard deviation)
Baseline (n=16, 17, 14, 3, 16)	4.858 ± 1.3027	5.567 ± 1.3314	6.188 ± 0.7897	4.700 ± 1.3604	5.123 ± 1.6435
Day 1 (n=16, 17, 14, 3, 17)	4.385 ± 1.6393	5.170 ± 1.4124	5.875 ± 1.4416	4.667 ± 0.4924	5.184 ± 1.6450
Day 2 (n=17, 14, 13, 3, 15)	4.184 ± 1.7204	4.503 ± 1.2868	5.376 ± 1.2581	4.477 ± 0.4879	4.531 ± 2.2140
Day 3 (n=2, 2, 2, 0, 0)	4.785 ± 1.3364	5.338 ± 2.6269	5.625 ± 0.2192	99999 ± 99999	99999 ± 99999
Day 4 (n=1, 0, 2, 0, 0)	4.940 ± 99999	99999 ± 99999	6.055 ± 1.1526	99999 ± 99999	99999 ± 99999
Day 5 (n=0, 0, 2, 0, 0)	99999 ± 99999	99999 ± 99999	4.665 ± 0.1344	99999 ± 99999	99999 ± 99999
Day 6 (n=0, 0, 1, 0, 0)	99999 ± 99999	99999 ± 99999	4.890 ± 99999	99999 ± 99999	99999 ± 99999
Day 7 (n=17, 15, 12, 2, 15)	2.134 ± 1.4451	2.469 ± 1.5193	3.808 ± 1.5745	2.756 ± 2.2688	2.751 ± 1.9724

No statistical analyses for this end point

Secondary: MAD: RSV viral RNA Concentrations in Nasal Swabs or Aspirates - FAS: Infected: Virology set

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End point title

MAD: RSV viral RNA Concentrations in Nasal Swabs or Aspirates - FAS: Infected: Virology set ^[69]

End point description

RSV viral RNA Concentrations in Nasal Swabs or Aspirates was assessed by quantitative RT-PCR. The FAS-IV population is defined to include all FAS-I subjects who have sufficient virology data for analysis. Subjects will be considered to not have sufficient virology data for analysis and will be removed from the FAS-IV population if Baseline viral load is <2 log10 PFUe/mL; Missing baseline viral load; Percent of intended volume administered is <50% for the loading dose or total maintenance dose or <3 viral load observations during the first 120 hours. Here, 'n' signifies the number of subjects analyzed at specified time point. Here "99999" indicates data was not evaluated at specified timepoint.

End point type

Secondary

End point timeframe

Baseline up to Day 28

Notes
[69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	12	5	13	12	13	25
Units: Log 10 PFUe/mL
arithmetic mean (standard deviation)
Baseline (n=5, 12, 5, 13, 12, 13, 25)	5.176 ± 1.0939	5.534 ± 1.6926	6.584 ± 0.9639	5.578 ± 1.3815	4.671 ± 1.1396	4.768 ± 0.8777	4.743 ± 1.3366
Day 1 (n=5, 12, 5, 13, 12, 13, 24)	4.528 ± 1.0248	5.386 ± 1.2769	5.760 ± 1.5262	4.668 ± 1.5975	4.051 ± 1.5294	4.079 ± 1.3464	4.348 ± 1.3836
Day 2 (5, 12, 5, 13, 10, 12, 25)	4.098 ± 1.2297	4.838 ± 1.6102	5.052 ± 1.5155	4.522 ± 1.4690	3.960 ± 1.9010	3.737 ± 0.8746	4.071 ± 1.5695
Day 3 (n=0, 2, 0, 1, 12, 11, 13)	99999 ± 99999	3.595 ± 1.9445	99999 ± 99999	6.460 ± 99999	3.118 ± 1.9139	3.129 ± 1.0418	3.000 ± 1.6639
Day 4 (0, 1, 0, 1, 7, 8, 11)	99999 ± 99999	2.900 ± 99999	99999 ± 99999	3.200 ± 99999	1.883 ± 1.3612	2.661 ± 1.3573	2.741 ± 1.5524
Day 5 (n=5, 12, 5, 13, 11, 13, 24)	2.658 ± 1.4290	3.807 ± 1.8995	4.408 ± 1.1502	3.514 ± 1.7953	1.646 ± 1.4766	2.608 ± 1.1903	2.598 ± 1.7806
Day 6 (n=0, 0, 0, 0, 6, 5, 2)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	1.062 ± 1.2809	2.452 ± 1.0368	1.355 ± 0.0212
Day 7 (n=0, 0, 0, 0, 2, 1, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	1.535 ± 0.2899	2.900 ± 99999	0.300 ± 99999
Day 8 (n=0, 0, 0, 0, 2, 1, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.930 ± 1.3152	1.790 ± 99999	2.720 ± 99999
Day 11 (n=5, 12, 4, 12, 12, 12, 24)	1.570 ± 1.2253	1.737 ± 1.5841	2.075 ± 1.6607	1.031 ± 1.2529	0.294 ± 0.6004	1.001 ± 1.7687	1.304 ± 1.4359
Day 28 (n=1, 1, 0, 7, 7, 5, 3)	5.230 ± 99999	0.020 ± 99999	99999 ± 99999	0.793 ± 1.0111	1.347 ± 1.8556	1.942 ± 2.6602	0.087 ± 0.1501

No statistical analyses for this end point

Secondary: MAD: RSV viral RNA Concentrations in Nasal Swabs or Aspirates - FAS: Infected

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End point title

MAD: RSV viral RNA Concentrations in Nasal Swabs or Aspirates - FAS: Infected ^[70]

End point description

RSV viral RNA Concentrations in Nasal Swabs or Aspirates was assessed by quantitative RT-PCR. FAS-I is defined to include all FAS subjects who are confirmed PCR positive for RSV viral RNA. Here, 'n' signifies the number of subjects analyzed at specified time point. Here "99999" indicates data was not evaluated at specified timepoint.

End point type

Secondary

End point timeframe

Baseline to Day 28

Notes
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	5	13	8	16	18	16	31
Units: Log 10 PFUe/mL
arithmetic mean (standard deviation)
Baseline (n=5, 13, 6, 16, 18, 16, 31)	5.176 ± 1.0939	5.212 ± 1.9932	5.765 ± 2.1835	5.120 ± 1.9784	4.676 ± 1.3800	4.743 ± 0.9484	4.460 ± 1.7332
Day 1 (n=5, 13, 8, 16, 17, 16, 28)	4.528 ± 1.0248	5.013 ± 1.8168	4.060 ± 2.8505	4.481 ± 1.7503	4.195 ± 1.4386	4.064 ± 1.3392	4.272 ± 1.5434
Day 2 (n=5, 13, 7, 15, 12, 15, 30)	4.098 ± 1.2297	4.556 ± 1.8455	4.326 ± 2.2737	4.113 ± 1.7465	3.971 ± 1.7865	3.709 ± 1.0221	4.034 ± 1.5983
Day 3 (n=0, 2, 0, 2, 14, 13, 14)	99999 ± 99999	3.595 ± 1.9445	99999 ± 99999	3.545 ± 4.1224	3.271 ± 1.8706	2.998 ± 1.1195	3.029 ± 1.6024
Day 4 (n=0, 1, 0, 2, 8, 11, 13)	99999 ± 99999	2.900 ± 99999	99999 ± 99999	2.620 ± 0.8202	2.054 ± 1.3498	2.685 ± 1.5268	2.670 ± 1.7043
Day 5 (n=5, 13, 8, 16, 14, 16, 29)	2.658 ± 1.4290	3.514 ± 2.1028	2.755 ± 2.4414	3.254 ± 1.8680	1.864 ± 1.7632	2.416 ± 1.2001	2.762 ± 1.9417
Day 6 (n=0, 0, 0, 1, 7, 6, 2)	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.720 ± 99999	1.357 ± 1.4065	2.043 ± 1.3645	1.355 ± 0.0212
Day 7 (n=0, 0, 0, 1, 3, 2, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	1.880 ± 99999	2.023 ± 0.8703	1.945 ± 1.3506	0.300 ± 99999
Day 8 (n=0, 0, 0, 0, 3, 1, 1)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.620 ± 1.0739	1.790 ± 99999	2.720 ± 99999
Day 9 (n=0, 0, 0, 0, 1, 0, 0)	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.000 ± 99999	99999 ± 99999	99999 ± 99999
Day 11 (n=5, 13, 7, 15, 17, 15, 29)	1.570 ± 1.2253	1.822 ± 1.5478	1.891 ± 1.4589	1.003 ± 1.1193	0.726 ± 1.5087	0.801 ± 1.6216	1.345 ± 1.4458
Day 28 (n=1, 1, 0, 8, 10, 7, 5)	5.230 ± 99999	0.020 ± 99999	99999 ± 99999	1.210 ± 1.5060	0.974 ± 1.6320	1.387 ± 2.3698	0.638 ± 1.2862

No statistical analyses for this end point

Secondary: SAD: Maximum Plasma Observed Concentration (Cmax) of ALS-008112 (JNJ-63549109)

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End point title

SAD: Maximum Plasma Observed Concentration (Cmax) of ALS-008112 (JNJ-63549109) ^[71]

End point description

Cmax is the maximum observed plasma concentration. Pharmacokinetics (PK) population was defined as all subjects that received one or more doses of ALS-008176 and with 1 quantifiable blood concentration.

End point type

Secondary

End point timeframe

On Day 1

Notes
[71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)
Number of subjects analysed	18	17	13	3
Units: nano-gram/milliliter (ng/ml)
arithmetic mean (geometric coefficient of variation)	129.5 ± 43.19	404.3 ± 63	1269 ± 55.86	1909 ± 20.91

No statistical analyses for this end point

Secondary: SAD: Area Under Curve (AUC) of ALS-008112 (JNJ-63549109)

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End point title

SAD: Area Under Curve (AUC) of ALS-008112 (JNJ-63549109) ^[72]

End point description

AUC is the area under plasma concentration curve. PK population was defined as all subjects that received one or more doses of ALS-008176 and with 1 quantifiable blood concentration.

End point type

Secondary

End point timeframe

On Day 1

Notes
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	SAD: ALS-008176 (1.37 mg/kg)	SAD: ALS-008176 (4.1 mg/kg)	SAD: ALS-008176 (12 mg/kg)	SAD: ALS-008176 (25 mg/kg)
Number of subjects analysed	18	17	13	3
Units: nanogramhour/milliliter (ngh/ml)
arithmetic mean (geometric coefficient of variation)	350.9 ± 14.89	959.9 ± 15.02	2574 ± 10.09	5122 ± 12.73

No statistical analyses for this end point

Secondary: MAD: Cmax of ALS-008112 (JNJ-63549109)

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End point title

MAD: Cmax of ALS-008112 (JNJ-63549109) ^[73]

End point description

Cmax is the maximum observed plasma concentration. PK population was defined as all subjects that received one or more doses of ALS-008176 and with 1 quantifiable blood concentration. Here 'n' signifies the number of subjects analyzed at specified time point.

End point type

Secondary

End point timeframe

Day 1 and Day 5

Notes
[73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)
Number of subjects analysed	5	14	8	17	18	16
Units: ng/ml
arithmetic mean (geometric coefficient of variation)
Day 1 (n=5, 14, 8, 17, 17, 16)	285 ± 25.81	867 ± 49.66	2431 ± 34.45	1895 ± 44.08	3142 ± 38.26	4653 ± 51.44
Day 5 (n=5, 14, 7, 16, 14, 16)	172.1 ± 29.09	211.8 ± 41.02	591.2 ± 44.23	991.3 ± 46.18	1867 ± 41.22	3380 ± 46.85

No statistical analyses for this end point

Secondary: MAD: AUC of ALS-008112 (JNJ-63549109)

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End point title

MAD: AUC of ALS-008112 (JNJ-63549109) ^[74]

End point description

AUC is area under plasma under curve. PK population was defined as all subjects that received one or more doses of ALS-008176 and with 1 quantifiable blood concentration. Here, 'n' signifies the number of subjects analyzed at specified time point.

End point type

Secondary

End point timeframe

On Day 1 and Day 5

Notes
[74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)
Number of subjects analysed	5	14	8	17	18	16
Units: ng*h/ml
arithmetic mean (geometric coefficient of variation)
Day 1 (5, 14, 8, 17, 17, 16)	1305 ± 10.04	2466 ± 11.34	6508 ± 8.843	7459 ± 15.62	10940 ± 11.88	16770 ± 10.28
Day 5 (n=5, 14, 7, 16, 14, 16)	1114 ± 7.467	1529 ± 8.405	3912 ± 8.483	6117 ± 7.843	10820 ± 13.76	18790 ± 9.45

No statistical analyses for this end point

Secondary: MAD: Number of Subjects with Emerging Genetic Variations in the RSV L Gene Considering the 4 Positions of Interest at the Last Evaluable On-treatment Time Point

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End point title

MAD: Number of Subjects with Emerging Genetic Variations in the RSV L Gene Considering the 4 Positions of Interest at the Last Evaluable On-treatment Time Point ^[75]

End point description

The emergence of genetic variations at RSV L amino acid positions 628, 789, 795, and 796 was evaluated. An emerging genetic variation is defined as a genetic variation (amino acid substitution, insertion or deletion) that is absent, that is with next-generation sequencing (NGS) read frequency <3%, at baseline but present with an NGS read frequency >= 15% at a later post-baseline time point. Safety Analysis Set defined as all randomized subjects who received at least 1 dose of study medication. Evaluable subjects for the secondary endpoint are subjects in the MAD Part with baseline and post-baseline RSV sequencing data available.

End point type

Secondary

End point timeframe

From Baseline to Day 28

Notes
[75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be reported for the specified arms only.

End point values	MAD: ALS-008176 (4.1/1.37 mg/kg)	MAD: ALS-008176 (10/2 mg/kg)	MAD: ALS-008176 (30/6 mg/kg)	MAD: ALS-008176 (30/10 mg/kg)	MAD: ALS-008176 (40/20 mg/kg)	MAD: ALS-008176 (60/40 mg/kg)	MAD: Placebo
Number of subjects analysed	3	8	3	4	13	9	13
Units: Subjects
number (not applicable)	0	0	0	0	0	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Approximately 4 years

Adverse event reporting additional description

Safety Analysis Set defined as all randomized subjects who received at least 1 dose of study medication. Some grade 3 and grade 4 low neutrophil counts were not reported as Adverse Events.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

Single dose of ALS-008176 (1.37 mg/kg)

Reporting group description

Subjects received single oral dose of 1.37 milligrams per kilogram (mg/kg) of ALS-008176.

Reporting group title

Single dose of ALS-008176 (4.1 mg/kg)

Reporting group description

Subjects received single oral dose of 4.1 mg/kg of ALS-008176.

Reporting group title

Single dose of ALS-008176 (12 mg/kg)

Reporting group description

Subjects received single oral dose of 12 mg/kg of ALS-008176.

Reporting group title

Single dose of ALS-008176 (25 mg/kg)

Reporting group description

Subjects received single oral dose of 25 mg/kg of ALS-008176.

Reporting group title

Multiple dose of ALS-008176 (4.1/1.37 mg/kg)

Reporting group description

Subjects received 1 loading dose of 4.1 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 1.37 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

Multiple dose of ALS-008176 (10/2 mg/kg)

Reporting group description

Subjects received loading dose of 10 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 2 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

Multiple dose of ALS-008176 (30/6 mg/kg)

Reporting group description

Subjects received loading dose of 30 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 6 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

Multiple dose of ALS-008176 (30/10 mg/kg)

Reporting group description

Subjects received loading dose of 30 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 10 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

Multiple dose of ALS-008176 (40/20 mg/kg)

Reporting group description

Subjects received loading dose of 40 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 20 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

Multiple dose of ALS-008176 (60/40 mg/kg)

Reporting group description

Subjects received loading dose of 60 mg/kg of ALS-008176 for dose 1 on Day 1 followed by 9 doses of 40 mg/kg of ALS-008176 twice daily for 5 consecutive days.

Reporting group title

Placebo

Reporting group description

Subjects received single and multiple doses of Placebo orally.

Serious adverse events	Single dose of ALS-008176 (1.37 mg/kg)	Single dose of ALS-008176 (4.1 mg/kg)	Single dose of ALS-008176 (12 mg/kg)	Single dose of ALS-008176 (25 mg/kg)	Multiple dose of ALS-008176 (4.1/1.37 mg/kg)	Multiple dose of ALS-008176 (10/2 mg/kg)	Multiple dose of ALS-008176 (30/6 mg/kg)	Multiple dose of ALS-008176 (30/10 mg/kg)	Multiple dose of ALS-008176 (40/20 mg/kg)	Multiple dose of ALS-008176 (60/40 mg/kg)	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	2 / 18 (11.11%)	0 / 16 (0.00%)	2 / 50 (4.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events
Vascular disorders
Phlebitis
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Sinus Tachycardia
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenitis
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia Bacterial
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Syncytial Virus Bronchiolitis
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Single dose of ALS-008176 (1.37 mg/kg)	Single dose of ALS-008176 (4.1 mg/kg)	Single dose of ALS-008176 (12 mg/kg)	Single dose of ALS-008176 (25 mg/kg)	Multiple dose of ALS-008176 (4.1/1.37 mg/kg)	Multiple dose of ALS-008176 (10/2 mg/kg)	Multiple dose of ALS-008176 (30/6 mg/kg)	Multiple dose of ALS-008176 (30/10 mg/kg)	Multiple dose of ALS-008176 (40/20 mg/kg)	Multiple dose of ALS-008176 (60/40 mg/kg)	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	13 / 18 (72.22%)	8 / 18 (44.44%)	6 / 14 (42.86%)	2 / 3 (66.67%)	4 / 5 (80.00%)	9 / 14 (64.29%)	4 / 8 (50.00%)	12 / 17 (70.59%)	12 / 18 (66.67%)	14 / 16 (87.50%)	22 / 50 (44.00%)
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	3 / 16 (18.75%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	1	3	0
Aspartate Aminotransferase Increased
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	1 / 14 (7.14%)	0 / 3 (0.00%)	1 / 5 (20.00%)	2 / 14 (14.29%)	0 / 8 (0.00%)	0 / 17 (0.00%)	3 / 18 (16.67%)	3 / 16 (18.75%)	2 / 50 (4.00%)
occurrences all number	1	0	1	0	1	2	0	0	3	3	2
Bilirubin Conjugated Increased
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Blood Alkaline Phosphatase Increased
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Blood Bicarbonate Decreased
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Blood Bilirubin Increased
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Blood Creatine Phosphokinase Increased
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	1 / 14 (7.14%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 50 (2.00%)
occurrences all number	1	0	1	0	1	0	0	0	0	0	1
Blood Potassium Increased
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Blood Pressure Diastolic Increased
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Blood Pressure Systolic Increased
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Cardiac Murmur
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 8 (12.50%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Electrocardiogram QT Prolonged
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Hepatic Enzyme Increased
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	1 / 14 (7.14%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	0
Lymphocyte Count Increased
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Monocyte Count Increased
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Neutrophil Count Decreased
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Platelet Count Increased
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	2 / 50 (4.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	2
Reticulocyte Count Increased
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	2 / 16 (12.50%)	1 / 50 (2.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	1
Weight Decreased
subjects affected / exposed	0 / 18 (0.00%)	1 / 18 (5.56%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
White Blood Cell Count Increased
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 50 (2.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	1
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Cardiac disorders
Bradycardia
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Sinus Tachycardia
subjects affected / exposed	0 / 18 (0.00%)	1 / 18 (5.56%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Tachycardia
subjects affected / exposed	0 / 18 (0.00%)	1 / 18 (5.56%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Ventricular Extrasystoles
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	1 / 14 (7.14%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 50 (2.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	1
Hyperleukocytosis
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Leukocytosis
subjects affected / exposed	0 / 18 (0.00%)	1 / 18 (5.56%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0
Neutropenia
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	2 / 18 (11.11%)	3 / 16 (18.75%)	1 / 50 (2.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	3	1
Thrombocytosis
subjects affected / exposed	4 / 18 (22.22%)	1 / 18 (5.56%)	1 / 14 (7.14%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 14 (7.14%)	1 / 8 (12.50%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	1 / 50 (2.00%)
occurrences all number	4	1	1	0	1	1	1	0	0	1	1
General disorders and administration site conditions
Instillation Site Swelling
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	2 / 18 (11.11%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0
Pyrexia
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	1 / 18 (5.56%)	1 / 16 (6.25%)	1 / 50 (2.00%)
occurrences all number	1	0	0	0	0	0	0	3	1	1	2
Eye disorders
Periorbital Oedema
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Gastrointestinal disorders
Abnormal Faeces
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Aphthous Ulcer
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Constipation
subjects affected / exposed	0 / 18 (0.00%)	1 / 18 (5.56%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Diarrhoea
subjects affected / exposed	2 / 18 (11.11%)	0 / 18 (0.00%)	1 / 14 (7.14%)	1 / 3 (33.33%)	2 / 5 (40.00%)	2 / 14 (14.29%)	1 / 8 (12.50%)	1 / 17 (5.88%)	2 / 18 (11.11%)	3 / 16 (18.75%)	5 / 50 (10.00%)
occurrences all number	2	0	1	1	2	2	1	2	2	3	5
Vomiting
subjects affected / exposed	2 / 18 (11.11%)	1 / 18 (5.56%)	0 / 14 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	1 / 14 (7.14%)	1 / 8 (12.50%)	3 / 17 (17.65%)	2 / 18 (11.11%)	5 / 16 (31.25%)	2 / 50 (4.00%)
occurrences all number	3	1	0	1	0	1	1	5	3	9	2
Hepatobiliary disorders
Hepatocellular Injury
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 50 (2.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	3
Rhinorrhoea
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	1 / 16 (6.25%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0
Upper Respiratory Tract Inflammation
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Skin and subcutaneous tissue disorders
Dermatitis Contact
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0
Dermatitis Diaper
subjects affected / exposed	0 / 18 (0.00%)	1 / 18 (5.56%)	0 / 14 (0.00%)	0 / 3 (0.00%)	2 / 5 (40.00%)	2 / 14 (14.29%)	1 / 8 (12.50%)	1 / 17 (5.88%)	0 / 18 (0.00%)	3 / 16 (18.75%)	4 / 50 (8.00%)
occurrences all number	0	1	0	0	2	2	1	1	0	3	4
Dry Skin
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0
Eczema
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	2 / 5 (40.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	1 / 17 (5.88%)	1 / 18 (5.56%)	1 / 16 (6.25%)	1 / 50 (2.00%)
occurrences all number	1	0	0	0	2	1	0	1	1	1	1
Eczema Infantile
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Erythema
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	2 / 17 (11.76%)	1 / 18 (5.56%)	0 / 16 (0.00%)	1 / 50 (2.00%)
occurrences all number	1	0	0	0	0	0	0	2	2	0	1
Miliaria
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0
Rash
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	1 / 14 (7.14%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	1 / 16 (6.25%)	2 / 50 (4.00%)
occurrences all number	1	0	1	0	0	1	0	0	1	1	2
Rash Erythematous
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Rash Macular
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Rash Papular
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 8 (12.50%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Seborrhoeic Dermatitis
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Skin Lesion
subjects affected / exposed	1 / 18 (5.56%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Skin Reaction
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 50 (2.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1
Infections and infestations
Adenovirus Infection
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Bronchitis
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	1 / 50 (2.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1
Candida Infection
subjects affected / exposed	0 / 18 (0.00%)	1 / 18 (5.56%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	1 / 18 (5.56%)	1 / 18 (5.56%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 8 (12.50%)	0 / 17 (0.00%)	0 / 18 (0.00%)	1 / 16 (6.25%)	1 / 50 (2.00%)
occurrences all number	1	1	0	0	0	0	1	0	0	1	1
Eye Infection Bacterial
subjects affected / exposed	0 / 18 (0.00%)	1 / 18 (5.56%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	1 / 16 (6.25%)	4 / 50 (8.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	5
Otitis Media Acute
subjects affected / exposed	0 / 18 (0.00%)	1 / 18 (5.56%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Otitis Media Viral
subjects affected / exposed	0 / 18 (0.00%)	1 / 18 (5.56%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Pneumonia Bacterial
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	1 / 14 (7.14%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	1 / 50 (2.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	1
Respiratory Syncytial Virus Bronchiolitis
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Tinea Infection
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Tonsillitis
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Upper Respiratory Tract Infection
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	2 / 50 (4.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	2
Urinary Tract Infection
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Viral Rash
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Viral Upper Respiratory Tract Infection
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 17 (5.88%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Metabolism and nutrition disorders
Fluid Overload
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Hyperglycaemia
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 17 (0.00%)	0 / 18 (0.00%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Hypokalaemia
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Hypomagnesaemia
subjects affected / exposed	0 / 18 (0.00%)	0 / 18 (0.00%)	0 / 14 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 17 (0.00%)	1 / 18 (5.56%)	0 / 16 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

19 Dec 2013

Instituted sentinel groups and age de-escalation; refined age strata.

17 Dec 2014

Independent Data Monitoring Committee (IDMC) authorized to change doses to be studied within defined limits; eligibility criteria related to hospitalization duration, Respiratory syncytial virus (RSV) symptoms duration, and concomitant medications updated.

24 Aug 2015

Follow up Day 28 visit added; initial Japanese Multiple ascending dose (MAD) cohort will be a lower dose than subjects in rest of world; RSV diagnosis for eligibility can be performed using any RSV assay; allowance of corticosteroids clarified; IDMC authorized to determine appropriate timing for transition from single ascending dose (SAD) to MAD part of study.

22 Jan 2016

Added cohort of neonate subjects; allow every 12 hours or twice daily dosing; disallow substrates for Organic Anion Transporter 3 (OAT3) transporter and RSV prophylactic medications.

13 Sep 2016

Potential additional cohorts added; further defined IDMC authority for decision making within defined limits; Japanese subjects will now be dosed at same dose levels as subjects in rest of world; Nasal aspirate changed to nasal swab procedure; updated eligibility criteria related to RSV symptoms duration; study drug can be administered without regard to food.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
10 Dec 2016	Enrollment paused for evaluation of neutropenia	12 May 2017

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: SAD: Number of Subjects with Treatment Emergent Adverse Events (TEAEs)

Primary: SAD: Number of Subjects with Treatment Emergent Adverse Events (TEAEs)

Primary: SAD: Change From Baseline in Physical Examination (Temperature)

Primary: SAD: Change From Baseline in Physical Examination (Temperature)

Primary: SAD: Change From Baseline for Physical Examination (Respiratory Rate)

Primary: SAD: Change From Baseline for Physical Examination (Respiratory Rate)

Primary: SAD: Change From Baseline in Physical Examination (Heart Rate)

Primary: SAD: Change From Baseline in Physical Examination (Heart Rate)

Primary: SAD: Change From Baseline in Physical Examination (Weight)

Primary: SAD: Change From Baseline in Physical Examination (Weight)

Primary: SAD: Change From Baseline in Physical Examination (Body Mass Index [BMI])

Primary: SAD: Change From Baseline in Physical Examination (Body Mass Index [BMI])

Primary: SAD: Change From Baseline in Physical Examination (Blood Pressure: Systolic Blood Pressure [sBP] and Distolic Blood Pressure [dBP])

Primary: SAD: Change From Baseline in Physical Examination (Blood Pressure: Systolic Blood Pressure [sBP] and Distolic Blood Pressure [dBP])

Primary: SAD: Change From Baseline for 12-lead Electrocardiogram (ECG) Parameters

Primary: SAD: Change From Baseline for 12-lead Electrocardiogram (ECG) Parameters

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Alkaline Phosphatase [AP], Alanine Aminotransferase [ALA], Aspartate Aminotransferase [ASA], Creatine Kinase [CrK])

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Alkaline Phosphatase [AP], Alanine Aminotransferase [ALA], Aspartate Aminotransferase [ASA], Creatine Kinase [CrK])

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Bilirubin, Direct Bilirubin [DB], and Indirect Bilirubin [IB], Creatinine [Cr])

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Bilirubin, Direct Bilirubin [DB], and Indirect Bilirubin [IB], Creatinine [Cr])

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Blood Urea Nitrogen [BUN], Derived Urea [DU], Chloride [Cl], Bicarbonate [BiC], Glucose [Glu], Potassium [K], Sodium[Na])

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Blood Urea Nitrogen [BUN], Derived Urea [DU], Chloride [Cl], Bicarbonate [BiC], Glucose [Glu], Potassium [K], Sodium[Na])

Primary: SAD: Change From Baseline in Clinical laboratory Parameter (Hematology-Reticulocyte Absolute [RA], Platelets [Pl], Leukocytes [LU], Monocytes [MO], Neutrophils [NE])

Primary: SAD: Change From Baseline in Clinical laboratory Parameter (Hematology-Reticulocyte Absolute [RA], Platelets [Pl], Leukocytes [LU], Monocytes [MO], Neutrophils [NE])

Primary: SAD: Change From Baseline in Reticulocyte Percent, Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, and Lymphocytes/Leukocytes

Primary: SAD: Change From Baseline in Reticulocyte Percent, Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, and Lymphocytes/Leukocytes

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin)

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin)

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration)

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration)

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology: Erythrocytes Mean Corpuscular Volume [e-MCV] and Mean Platelet Volume [MPV])

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology: Erythrocytes Mean Corpuscular Volume [e-MCV] and Mean Platelet Volume [MPV])

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology: Erythrocytes Distribution Width)

Primary: SAD: Change From Baseline in Clinical Laboratory Parameter (Hematology: Erythrocytes Distribution Width)

Primary: MAD: Change From Baseline in Physical Examination (Temperature)

Primary: MAD: Change From Baseline in Physical Examination (Temperature)

Primary: MAD: Change From Baseline in Physical Examination (Respiratory Rate)

Primary: MAD: Change From Baseline in Physical Examination (Respiratory Rate)

Primary: MAD: Change From Baseline in Physical Examination (Heart Rate)

Primary: MAD: Change From Baseline in Physical Examination (Heart Rate)

Primary: MAD: Change From Baseline in Physical Examination (Weight)

Primary: MAD: Change From Baseline in Physical Examination (Weight)

Primary: MAD: Change From Baseline in Physical Examination (BMI)

Primary: MAD: Change From Baseline in Physical Examination (BMI)

Primary: MAD: Change From Baseline for Vital signs (Blood Pressure: sBP and dBP)

Primary: MAD: Change From Baseline for Vital signs (Blood Pressure: sBP and dBP)

Primary: MAD: Change From Baseline in ECG Parameters

Primary: MAD: Change From Baseline in ECG Parameters

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter: Serum Chemistry-Alkaline Phosphatase (AP), Alanine Aminotransferase (ALA), Aspartate Aminotransferase (ASA), Creatine Kinase (CrK)

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter: Serum Chemistry-Alkaline Phosphatase (AP), Alanine Aminotransferase (ALA), Aspartate Aminotransferase (ASA), Creatine Kinase (CrK)

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Bilirubin, Direct [DB], Indirect bilirubin [IB], and Creatinine [Cr])

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Bilirubin, Direct [DB], Indirect bilirubin [IB], and Creatinine [Cr])

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Blood Urea nitrogen [BUN], Derived Urea [DU], Chloride [Cl], Bicarbonate [BiC], Glucose [Glu], Potassium [K], Sodium [Na])

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Serum Chemistry-Blood Urea nitrogen [BUN], Derived Urea [DU], Chloride [Cl], Bicarbonate [BiC], Glucose [Glu], Potassium [K], Sodium [Na])

Primary: MAD: Change From Baseline in Clinical laboratory Parameter (Hematology-Reticulocyte Absolute [RA], Platelets [Pl], Leukocytes [LU], Monocytes [MO], Neutrophils [NE])

Primary: MAD: Change From Baseline in Clinical laboratory Parameter (Hematology-Reticulocyte Absolute [RA], Platelets [Pl], Leukocytes [LU], Monocytes [MO], Neutrophils [NE])

Primary: MAD: Change From Baseline in Reticulocyte Percent, Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, and Lymphocytes/Leukocytes

Primary: MAD: Change From Baseline in Reticulocyte Percent, Hematocrit, Basophils/Leukocytes, Eosinophils/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, and Lymphocytes/Leukocytes

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin)

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular Hemoglobin)

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular HGB Concentration)

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Hematology- Erythrocytes Mean Corpuscular HGB Concentration)

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Erythrocytes Mean Corpuscular Volume [e-MCV] and Mean Platelet Volume [MPV])

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Erythrocytes Mean Corpuscular Volume [e-MCV] and Mean Platelet Volume [MPV])

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Erythrocytes Distribution Width)

Primary: MAD: Change From Baseline in Clinical Laboratory Parameter (Erythrocytes Distribution Width)

Secondary: SAD: Respiratory Syncytial Virus (RSV) viral Ribonucleic Acid (RNA) Concentrations in Nasal Swabs or Aspirates - FAS Infected: Virology Set

Secondary: SAD: Respiratory Syncytial Virus (RSV) viral Ribonucleic Acid (RNA) Concentrations in Nasal Swabs or Aspirates - FAS Infected: Virology Set

Secondary: SAD: RSV viral RNA Concentrations in Nasal Swabs or Aspirates - FAS: Infected

Secondary: SAD: RSV viral RNA Concentrations in Nasal Swabs or Aspirates - FAS: Infected

Secondary: MAD: RSV viral RNA Concentrations in Nasal Swabs or Aspirates - FAS: Infected: Virology set