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Clinical Trial Results:
A Phase I/II, Multicenter, Open-Label, Noncomparative Study of the International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Group to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiretroviral Activity of Raltegravir (Isentress™, MK-0518) in HIV-1 Infected Children and Adolescents

Summary
EudraCT number	2009-015884-15
Trial protocol	Outside EU/EEA
Global end of trial date	17 May 2017

Results information
Results version number	v1(current)
This version publication date	25 Nov 2017
First version publication date	25 Nov 2017
Other versions

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

0518-022

ISRCTN number

US NCT number

NCT00485264

WHO universal trial number (UTN)

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000279-PIP01-08

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

17 May 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 May 2017

Was the trial ended prematurely?

Main objective of the trial

The main objective of this study was to evaluate in infants, children and adolescents the following: 1) the short term safety and tolerability of raltegravir; 2) the steady state plasma concentration profiles and pharmacokinetic parameters of raltegravir; 3) in chronic dosing, to evaluate the safety and tolerability of raltegravir at a selected dose in combination with optimized background therapy (OBT).

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

For Cohorts I, IIA, IIB and III stable background Highly Active Antiretroviral Therapy (HAART) is defined as unchanged therapeutic regimen for at least 12 weeks, or treatment experienced (not including therapy to interrupt maternal-infant transmission) but on no treatment for ≥ 4 weeks prior to entry. For Cohort IV, a participant must have received therapy to either interrupt maternal-infant transmission and/or to treat HIV infection. For Cohort V, the participant must have received therapy to interrupt maternal-infant transmission, but have not received other anti-HIV therapies.

Evidence for comparator

Actual start date of recruitment

11 Sep 2009

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

4 Years

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 1

Country: Number of subjects enrolled

Botswana: 3

Country: Number of subjects enrolled

Brazil: 12

Country: Number of subjects enrolled

South Africa: 27

Country: Number of subjects enrolled

United States: 110

Worldwide total number of subjects

153

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)

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

Children and adolescents ages ≥ 4 weeks to <19 years that were infected with HIV-1 were enrolled in this study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort I: 200 to 600 mg Raltegravir PFC tablets BID

Arm description

Participants ≥ 12 to <19 years of age who received a weight based dose of 200 mg to 600 mg raltegravir poloxamer film coated (PFC) tablets twice daily (BID). After dose selection all participants received 400 mg raltegravir PFC BID.

Arm type

Experimental

Investigational medicinal product name

Raltegravir

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Weight based dose of 200 to 600 mg raltegravir PFC BID. After dose selection, all participants received 400 mg raltegravir PFC BID.

Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID

Arm description

Participants ≥ 6 to <12 years of age who received a weight based dose of 200 mg to 400 mg raltegravir PFC tablets BID. After dose selection all participants >=25 kg received 400 mg raltegravir PFC BID.

Arm type

Experimental

Investigational medicinal product name

Raltegravir

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Weight based dose of 200 to 400 mg raltegravir PFC BID. After dose selection, all participants >=25 kg received 400 mg raltegravir PFC BID. Participants <25 kg received a weight based dose of the raltegravir CH BID.

Cohort IIB: ~ 6-8 mg/kg Raltegravir CH tablets BID

Arm description

Participants ≥ 6 to <12 years of age who received a weight based dose of ~6 mg to 8 mg/kg raltegravir chewable (CH) tablets BID. After dose selection all participants received a weight based dose of ~6 mg/kg raltegravir CH BID.

Arm type

Experimental

Investigational medicinal product name

Raltegravir

Investigational medicinal product code

Other name

Pharmaceutical forms

Chewable tablet

Routes of administration

Oral use

Dosage and administration details

Weight based dose of ~6 mg to 8 mg/kg raltegravir CH tablets BID. After dose selection all participants received a weight based dose of ~6 mg/kg raltegravir CH BID.

Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID

Arm description

Participants ≥ 2 to <6 years of age who received a weight based dose of ~6 mg/kg raltegravir CH tablets BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Arm type

Experimental

Investigational medicinal product name

Raltegravir

Investigational medicinal product code

Other name

Pharmaceutical forms

Chewable tablet

Routes of administration

Oral use

Dosage and administration details

Weight based dose of ~6 mg/kg raltegravir CH tablets BID.

Cohort IV: ~ 6 mg/kg Raltegravir OGS BID

Arm description

Participants ≥ 6 months to <2 years of age who received a weight based dose of ~6 mg/kg raltegravir oral granules for suspension (OGS) BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Arm type

Experimental

Investigational medicinal product name

Raltegravir

Investigational medicinal product code

Other name

Pharmaceutical forms

Granules

Routes of administration

Oral use

Dosage and administration details

Weight based dose of ~6 mg/kg raltegravir OGS BID.

Cohort V: ~ 6 mg/kg Raltegravir OGS BID

Arm description

Participants ≥ 4 weeks to <6 months of age who received a weight based dose of ~6 mg/kg raltegravir OGS BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Arm type

Experimental

Investigational medicinal product name

Raltegravir

Investigational medicinal product code

Other name

Pharmaceutical forms

Granules

Routes of administration

Oral use

Dosage and administration details

Weight based dose of ~6 mg/kg raltegravir OGS BID.

Number of subjects in period 1	Cohort I: 200 to 600 mg Raltegravir PFC tablets BID	Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID	Cohort IIB: ~ 6-8 mg/kg Raltegravir CH tablets BID	Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID	Cohort IV: ~ 6 mg/kg Raltegravir OGS BID	Cohort V: ~ 6 mg/kg Raltegravir OGS BID
Started	71	16	18	21	15	12
Completed	48	12	17	19	10	6
Not completed	23	4	1	2	5	6
Adverse event, serious fatal	1	-	-	-	1	-
Consent withdrawn by subject	4	1	-	-	1	-
Met study objective	-	1	-	1	-	-
Unable to contact	3	1	1	-	-	-
Not Treated	-	-	-	-	1	-
Unknown	1	-	-	-	-	-
Cannot get to clinic	6	-	-	1	1	2
Unwilling to follow requirements	8	1	-	-	1	-
Study site closed	-	-	-	-	-	4

Baseline characteristics

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Reporting group title

Cohort I: 200 to 600 mg Raltegravir PFC tablets BID

Reporting group description

Reporting group title

Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID

Reporting group description

Reporting group title

Cohort IIB: ~ 6-8 mg/kg Raltegravir CH tablets BID

Reporting group description

Reporting group title

Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID

Reporting group description

Participants ≥ 2 to <6 years of age who received a weight based dose of ~6 mg/kg raltegravir CH tablets BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Reporting group title

Cohort IV: ~ 6 mg/kg Raltegravir OGS BID

Reporting group description

Reporting group title

Cohort V: ~ 6 mg/kg Raltegravir OGS BID

Reporting group description

Participants ≥ 4 weeks to <6 months of age who received a weight based dose of ~6 mg/kg raltegravir OGS BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Reporting group values	Cohort I: 200 to 600 mg Raltegravir PFC tablets BID	Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID	Cohort IIB: ~ 6-8 mg/kg Raltegravir CH tablets BID	Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID	Cohort IV: ~ 6 mg/kg Raltegravir OGS BID	Cohort V: ~ 6 mg/kg Raltegravir OGS BID	Total
Number of subjects	71	16	18	21	15	12	153
Age Categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	15	12	27
Children (2-11 years)	0	16	18	21	0	0	55
Adolescents (12-17 years)	60	0	0	0	0	0	60
Adults (18-64 years)	11	0	0	0	0	0	11
From 65-84 years	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	15 ( 2.0 )	9.1 ( 1.6 )	8.9 ( 1.6 )	3.1 ( 1.2 )	1.0 ( 0.5 )	0.3 ( 0.1 )	-
Gender Categorical
Units: Subjects
Female	34	7	7	13	5	4	70
Male	37	9	11	8	10	8	83
Age Continuous
Units: Years
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )	-

Subject analysis set title

Cohort I: 200 to 600 mg Raltegravir PFC tablets BID

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID

Subject analysis set type

Safety analysis

Subject analysis set description

Participants ≥ 2 to <6 years of age who received a weight based dose of ~6 mg/kg raltegravir CH tablets BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Subject analysis set title

Cohort IV: ~ 6 mg/kg Raltegravir OGS BID

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Cohort V: ~ 6 mg/kg Raltegravir OGS BID

Subject analysis set type

Safety analysis

Subject analysis set description

Participants ≥ 4 weeks to <6 months of age who received a weight based dose of ~6 mg/kg raltegravir OGS BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Subject analysis sets values	Cohort I: 200 to 600 mg Raltegravir PFC tablets BID	Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID	Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID	Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID	Cohort IV: ~ 6 mg/kg Raltegravir OGS BID	Cohort V: ~ 6 mg/kg Raltegravir OGS BID
Number of subjects	71	16	18	21	14	12
Age Categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	15	12
Children (2-11 years)	0	16	18	21	0	0
Adolescents (12-17 years)	60	0	0	0	0	0
Adults (18-64 years)	11	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )
Gender Categorical
Units: Subjects
Female	34	7	7	13	5	4
Male	37	9	11	8	9	8
Age Continuous
Units: Years
arithmetic mean (standard deviation)	15 ( 2 )	9.1 ( 1.6 )	8.9 ( 1.6 )	3.1 ( 1.2 )	1.0 ( 0.5 )	0.3 ( 0.1 )

End points

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Reporting group title

Cohort I: 200 to 600 mg Raltegravir PFC tablets BID

Reporting group description

Reporting group title

Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID

Reporting group description

Reporting group title

Cohort IIB: ~ 6-8 mg/kg Raltegravir CH tablets BID

Reporting group description

Reporting group title

Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID

Reporting group description

Participants ≥ 2 to <6 years of age who received a weight based dose of ~6 mg/kg raltegravir CH tablets BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Reporting group title

Cohort IV: ~ 6 mg/kg Raltegravir OGS BID

Reporting group description

Reporting group title

Cohort V: ~ 6 mg/kg Raltegravir OGS BID

Reporting group description

Participants ≥ 4 weeks to <6 months of age who received a weight based dose of ~6 mg/kg raltegravir OGS BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Subject analysis set title

Cohort I: 200 to 600 mg Raltegravir PFC tablets BID

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID

Subject analysis set type

Safety analysis

Subject analysis set description

Participants ≥ 2 to <6 years of age who received a weight based dose of ~6 mg/kg raltegravir CH tablets BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Subject analysis set title

Cohort IV: ~ 6 mg/kg Raltegravir OGS BID

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Cohort V: ~ 6 mg/kg Raltegravir OGS BID

Subject analysis set type

Safety analysis

Subject analysis set description

Participants ≥ 4 weeks to <6 months of age who received a weight based dose of ~6 mg/kg raltegravir OGS BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Primary: Number of participants with one or more adverse events (AEs)

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End point title

Number of participants with one or more adverse events (AEs) ^[1]

End point description

An AE is any untoward medical occurrence in a participant administered a study agent and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. The population analyzed was all participants who received at least one dose of raltegravir.

End point type

Primary

End point timeframe

Up to week 269

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: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint.

End point values	Cohort I: 200 to 600 mg Raltegravir PFC tablets BID	Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID	Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID	Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID	Cohort IV: ~ 6 mg/kg Raltegravir OGS BID	Cohort V: ~ 6 mg/kg Raltegravir OGS BID
Number of subjects analysed	71	16	18	21	14	12
Units: Participants
number (not applicable)	69	16	18	21	14	12

No statistical analyses for this end point

Primary: Number of participants who discontinued study medication due to an AE

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End point title

Number of participants who discontinued study medication due to an AE ^[2]

End point description

End point type

Primary

End point timeframe

Up to week 269

Notes
[2] - 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: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint

End point values	Cohort I: 200 to 600 mg Raltegravir PFC tablets BID	Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID	Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID	Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID	Cohort IV: ~ 6 mg/kg Raltegravir OGS BID	Cohort V: ~ 6 mg/kg Raltegravir OGS BID
Number of subjects analysed	71	16	18	21	14	12
Units: Participants
number (not applicable)	0	0	0	0	0	1

No statistical analyses for this end point

Primary: Area under the concentration-time curve from time 0-12 hours post-dose for plasma raltegravir (AUC0-12h)

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End point title

Area under the concentration-time curve from time 0-12 hours post-dose for plasma raltegravir (AUC0-12h) ^[3]

End point description

Blood samples were collected for intensive pharmacokinetics (PK) between Days 5 and 12 following the initial raltegravir dose. If repeat intensive PK was required, it was collected between Days 7 and 14 following the raltegravir dose adjustment. The raltegravir AUC0-12 was determined using non-compartmental analysis.

End point type

Primary

End point timeframe

Cohorts I, IIA, IIB and III: pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post dose; Cohort IV: pre-dose, 0.5, 1, 2, 4 and 12 hours post dosing; Cohort V: pre-dose, 0.5, 1, 3-5, and 8-10 hours post dosing.

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: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint

End point values	Cohort I: 200 to 600 mg Raltegravir PFC tablets BID	Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID	Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID	Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID	Cohort IV: ~ 6 mg/kg Raltegravir OGS BID	Cohort V: ~ 6 mg/kg Raltegravir OGS BID
Number of subjects analysed	11	11	10	12	8	11
Units: µM*hr
geometric mean (geometric coefficient of variation)	15.71 ( 98 )	15.84 ( 120 )	22.58 ( 34 )	17.95 ( 59 )	19.8 ( 34.3 )	22.3 ( 40.2 )

No statistical analyses for this end point

Primary: Maximum concentration of plasma raltegravir (Cmax)

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End point title

Maximum concentration of plasma raltegravir (Cmax) ^[4]

End point description

Blood samples were collected for intensive PK between Days 5 and 12 following the initial raltegravir dose. If repeat intensive PK was required, it was collected between Days 7 and 14 following the raltegravir dose adjustment. The raltegravir Cmax was determined using non-compartmental analysis.

End point type

Primary

End point timeframe

Notes
[4] - 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: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint

End point values	Cohort I: 200 to 600 mg Raltegravir PFC tablets BID	Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID	Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID	Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID	Cohort IV: ~ 6 mg/kg Raltegravir OGS BID	Cohort V: ~ 6 mg/kg Raltegravir OGS BID
Number of subjects analysed	11	11	10	12	8	11
Units: µM
geometric mean (geometric coefficient of variation)	4.00 ( 95 )	4.80 ( 130 )	10.49 ( 53 )	9.74 ( 57 )	10.6 ( 64.8 )	8.6 ( 38.7 )

No statistical analyses for this end point

Primary: Time to maximum concentration of plasma raltegravir (Tmax)

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End point title

Time to maximum concentration of plasma raltegravir (Tmax) ^[5]

End point description

Blood samples were collected for intensive PK between Days 5 and 12 following the initial raltegravir dose. If repeat intensive PK was required, it was collected between Days 7 and 14 following the raltegravir dose adjustment. The raltegravir Tmax was determined using non-compartmental analysis.

End point type

Primary

End point timeframe

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: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint

End point values	Cohort I: 200 to 600 mg Raltegravir PFC tablets BID	Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID	Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID	Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID	Cohort IV: ~ 6 mg/kg Raltegravir OGS BID	Cohort V: ~ 6 mg/kg Raltegravir OGS BID
Number of subjects analysed	11	11	10	12	8	11
Units: hr
arithmetic mean (standard deviation)	1.8 ( 1.8 )	2.3 ( 0.9 )	0.7 ( 0.2 )	1.5 ( 1.3 )	0.82 ( 0.53 )	0.88 ( 0.33 )

No statistical analyses for this end point

Primary: Concentration at 12 hours post-dose of plasma raltegravir (C12hr)

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End point title

Concentration at 12 hours post-dose of plasma raltegravir (C12hr) ^[6]

End point description

Blood samples were collected for intensive PK between Days 5 and 12 following the initial raltegravir dose. If repeat intensive PK was required, it was collected between Days 7 and 14 following the raltegravir dose adjustment. The raltegravir C12hr was determined using non-compartmental analysis.

End point type

Primary

End point timeframe

12 hours post dose

Notes
[6] - 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: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint

End point values	Cohort I: 200 to 600 mg Raltegravir PFC tablets BID	Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID	Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID	Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID	Cohort IV: ~ 6 mg/kg Raltegravir OGS BID	Cohort V: ~ 6 mg/kg Raltegravir OGS BID
Number of subjects analysed	11	11	10	12	8	11
Units: nM
geometric mean (geometric coefficient of variation)	333 ( 78 )	246 ( 221 )	130 ( 88 )	71 ( 55 )	108.2 ( 52.3 )	116.6 ( 67.7 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to week 269

Adverse event reporting additional description

All participants who received at least one dose of raltegravir

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Cohort I: 200 to 600 mg Raltegravir PFC tablets BID

Reporting group description

Participants ≥ 12 to <19 years of age who received a weight based dose of 200 mg to 600 mg raltegravir PFC) tablets BID. After dose selection all participants received 400 mg raltegravir PFC BID.

Reporting group title

Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID

Reporting group description

Reporting group title

Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID

Reporting group description

Reporting group title

Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID

Reporting group description

Participants ≥ 2 to <6 years of age who received a weight based dose of ~6 mg/kg raltegravir CH tablets BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Reporting group title

Cohort IV: ~ 6 mg/kg Raltegravir OGS BID

Reporting group description

Reporting group title

Cohort V: ~ 6 mg/kg Raltegravir OGS BID

Reporting group description

Participants ≥ 4 weeks to <6 months of age who received a weight based dose of ~6 mg/kg raltegravir OGS BID. Dose selection confirmed the ~6mg/kg dose thus all participants continued at this dose.

Serious adverse events	Cohort I: 200 to 600 mg Raltegravir PFC tablets BID	Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID	Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID	Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID	Cohort IV: ~ 6 mg/kg Raltegravir OGS BID	Cohort V: ~ 6 mg/kg Raltegravir OGS BID
Total subjects affected by serious adverse events
subjects affected / exposed	20 / 71 (28.17%)	1 / 16 (6.25%)	6 / 18 (33.33%)	4 / 21 (19.05%)	6 / 14 (42.86%)	4 / 12 (33.33%)
number of deaths (all causes)	1	0	0	0	1	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Vascular disorders
Hypovolaemic shock
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Lipoma excision
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
Social circumstances
Treatment noncompliance
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Reproductive system and breast disorders
Vaginal haemorrhage
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	2 / 14 (14.29%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Respiratory distress
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 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
Psychiatric disorders
Agitation
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Bipolar disorder
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Depression
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Suicidal behaviour
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
Investigations
Blood bilirubin increased
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lipase abnormal
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lipase increased
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Injury, poisoning and procedural complications
Post procedural complication
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Nervous system disorders
Febrile convulsion
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neurological symptom
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Seizure
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
Colitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Oesophagitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Hepatobiliary disorders
Drug-induced liver injury
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	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
Skin and subcutaneous tissue disorders
Dyshidrotic eczema
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 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
Rash
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	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
Rash erythematous
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	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
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Infections and infestations
Abdominal abscess
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute sinusitis
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Appendicitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	2 / 18 (11.11%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Infection
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Lower respiratory tract infection
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mastoiditis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 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
Meningitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mycobacterium avium complex infection
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Periorbital cellulitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Pneumocystis jirovecii pneumonia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	6 / 71 (8.45%)	0 / 16 (0.00%)	1 / 18 (5.56%)	2 / 21 (9.52%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 6	0 / 0	0 / 1	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 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
Respiratory tract infection viral
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 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
Sepsis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Septic shock
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Varicella
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Varicella zoster virus infection
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Metabolism and nutrition disorders
Cachexia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Failure to thrive
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Hyperglycaemia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Hypoglycaemia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Cohort I: 200 to 600 mg Raltegravir PFC tablets BID	Cohort IIA: 200 to 400 mg Raltegravir PFC tablets BID	Cohort IIB: ~ 6 to 8 mg/kg Raltegravir CH tablets BID	Cohort III: ~ 6 mg/kg Raltegravir CH tablets BID	Cohort IV: ~ 6 mg/kg Raltegravir OGS BID	Cohort V: ~ 6 mg/kg Raltegravir OGS BID
Total subjects affected by non serious adverse events
subjects affected / exposed	69 / 71 (97.18%)	16 / 16 (100.00%)	18 / 18 (100.00%)	21 / 21 (100.00%)	14 / 14 (100.00%)	12 / 12 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Lipoma
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Skin papilloma
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	2 / 18 (11.11%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	4	0	2	1	1	0
Uterine leiomyoma
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Hypotension
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Pallor
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Pregnancy, puerperium and perinatal conditions
First trimester pregnancy
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Pregnancy
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Chest discomfort
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	0	0
Chest pain
subjects affected / exposed	7 / 71 (9.86%)	2 / 16 (12.50%)	3 / 18 (16.67%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	2	3	0	0	0
Chills
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0	0
Crepitations
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Crying
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Cyst
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Fatigue
subjects affected / exposed	7 / 71 (9.86%)	1 / 16 (6.25%)	2 / 18 (11.11%)	2 / 21 (9.52%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	1	2	2	0	0
Influenza like illness
subjects affected / exposed	5 / 71 (7.04%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	5	0	1	0	1	0
Injection site mass
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Injection site oedema
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Local swelling
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Localised oedema
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Malaise
subjects affected / exposed	6 / 71 (8.45%)	0 / 16 (0.00%)	1 / 18 (5.56%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	6	0	1	1	0	0
Mass
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Nodule
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Oedema peripheral
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Pain
subjects affected / exposed	4 / 71 (5.63%)	1 / 16 (6.25%)	1 / 18 (5.56%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	1	1	1	0	0
Peripheral swelling
subjects affected / exposed	2 / 71 (2.82%)	1 / 16 (6.25%)	2 / 18 (11.11%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	2	0	0	0
Puncture site discharge
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Pyrexia
subjects affected / exposed	33 / 71 (46.48%)	10 / 16 (62.50%)	12 / 18 (66.67%)	10 / 21 (47.62%)	8 / 14 (57.14%)	6 / 12 (50.00%)
occurrences all number	33	10	12	10	8	6
Secretion discharge
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0	0
Tenderness
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Immune reconstitution inflammatory syndrome
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Social circumstances
Victim of sexual abuse
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Reproductive system and breast disorders
Breast discharge
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Breast pain
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Breast tenderness
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Cervical dysplasia
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0	0
Dysfunctional uterine bleeding
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Dysmenorrhoea
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Gynaecomastia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Haemorrhagic ovarian cyst
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Male sexual dysfunction
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Metrorrhagia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Perineal erythema
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Polycystic ovaries
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Testicular pain
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Testicular swelling
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Uterine haemorrhage
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Vaginal discharge
subjects affected / exposed	7 / 71 (9.86%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	7	1	0	0	1	0
Vaginal haemorrhage
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Vaginal odour
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Vaginal ulceration
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Vulvovaginal discomfort
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Vulvovaginal pruritus
subjects affected / exposed	1 / 71 (1.41%)	1 / 16 (6.25%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	1	0	0
Vulvovaginal rash
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	1	0	1	1	0
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Asthma
subjects affected / exposed	3 / 71 (4.23%)	1 / 16 (6.25%)	0 / 18 (0.00%)	2 / 21 (9.52%)	2 / 14 (14.29%)	0 / 12 (0.00%)
occurrences all number	3	1	0	2	2	0
Asthma exercise induced
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Atelectasis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Bronchial hyperreactivity
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	1 / 18 (5.56%)	2 / 21 (9.52%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	2	0	0
Cough
subjects affected / exposed	48 / 71 (67.61%)	11 / 16 (68.75%)	11 / 18 (61.11%)	16 / 21 (76.19%)	9 / 14 (64.29%)	10 / 12 (83.33%)
occurrences all number	48	11	11	16	9	10
Dysphonia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Dyspnoea
subjects affected / exposed	10 / 71 (14.08%)	0 / 16 (0.00%)	2 / 18 (11.11%)	1 / 21 (4.76%)	3 / 14 (21.43%)	2 / 12 (16.67%)
occurrences all number	10	0	2	1	3	2
Dyspnoea exertional
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Epistaxis
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	1	0	0	0
Haemoptysis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Hypoxia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Idiopathic interstitial pneumonia
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Nasal congestion
subjects affected / exposed	32 / 71 (45.07%)	6 / 16 (37.50%)	12 / 18 (66.67%)	8 / 21 (38.10%)	6 / 14 (42.86%)	9 / 12 (75.00%)
occurrences all number	32	6	12	8	6	9
Nasal discharge discolouration
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Nasal obstruction
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Nasal oedema
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Nasal pruritus
subjects affected / exposed	1 / 71 (1.41%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0	0
Nasal turbinate abnormality
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	1	0
Oropharyngeal discomfort
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	28 / 71 (39.44%)	6 / 16 (37.50%)	8 / 18 (44.44%)	2 / 21 (9.52%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	28	6	8	2	1	0
Oropharyngeal plaque
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0	0
Paranasal sinus discomfort
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Pharyngeal erythema
subjects affected / exposed	4 / 71 (5.63%)	1 / 16 (6.25%)	1 / 18 (5.56%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	4	1	1	1	1	0
Pharyngeal exudate
subjects affected / exposed	1 / 71 (1.41%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0	0
Pharyngeal inflammation
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Pharyngeal ulceration
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Pleural effusion
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Productive cough
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	1	0	0	0
Pulmonary congestion
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Pulmonary oedema
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Rales
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	2 / 14 (14.29%)	1 / 12 (8.33%)
occurrences all number	1	0	0	1	2	1
Respiratory distress
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Respiratory tract congestion
subjects affected / exposed	5 / 71 (7.04%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	0	1	0	0	0
Rhinorrhoea
subjects affected / exposed	26 / 71 (36.62%)	2 / 16 (12.50%)	9 / 18 (50.00%)	13 / 21 (61.90%)	6 / 14 (42.86%)	10 / 12 (83.33%)
occurrences all number	26	2	9	13	6	10
Rhonchi
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	1	0
Sinus congestion
subjects affected / exposed	2 / 71 (2.82%)	1 / 16 (6.25%)	0 / 18 (0.00%)	2 / 21 (9.52%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	2	0	0
Sinus pain
subjects affected / exposed	2 / 71 (2.82%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0	0
Sleep apnoea syndrome
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	1	0	0
Sneezing
subjects affected / exposed	3 / 71 (4.23%)	3 / 16 (18.75%)	1 / 18 (5.56%)	2 / 21 (9.52%)	2 / 14 (14.29%)	1 / 12 (8.33%)
occurrences all number	3	3	1	2	2	1
Snoring
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Sputum discoloured
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Tachypnoea
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Tonsillar hypertrophy
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	2 / 18 (11.11%)	0 / 21 (0.00%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	0	0	2	0	1	1
Tonsillar inflammation
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Upper-airway cough syndrome
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Wheezing
subjects affected / exposed	12 / 71 (16.90%)	4 / 16 (25.00%)	3 / 18 (16.67%)	4 / 21 (19.05%)	3 / 14 (21.43%)	0 / 12 (0.00%)
occurrences all number	12	4	3	4	3	0
Psychiatric disorders
Abnormal behaviour
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	1	0	0	0
Adjustment disorder
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0	0
Agitation
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Anger
subjects affected / exposed	3 / 71 (4.23%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	1	0	0	0	0
Anxiety
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0	0
Attention deficit/hyperactivity disorder
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Autism spectrum disorder
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Conduct disorder
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Depression
subjects affected / exposed	8 / 71 (11.27%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	8	0	1	0	0	0
Generalised anxiety disorder
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Hallucination, auditory
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Initial insomnia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Insomnia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Learning disorder
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Major depression
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0	0
Mental status changes
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Mood swings
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0	0
Nightmare
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Oppositional defiant disorder
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Post-traumatic stress disorder
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Psychotic disorder
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Reading disorder
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Restlessness
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Sexually inappropriate behaviour
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Sleep terror
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	20 / 71 (28.17%)	2 / 16 (12.50%)	6 / 18 (33.33%)	4 / 21 (19.05%)	1 / 14 (7.14%)	3 / 12 (25.00%)
occurrences all number	20	2	6	4	1	3
Aspartate aminotransferase increased
subjects affected / exposed	15 / 71 (21.13%)	3 / 16 (18.75%)	4 / 18 (22.22%)	5 / 21 (23.81%)	4 / 14 (28.57%)	3 / 12 (25.00%)
occurrences all number	15	3	4	5	4	3
Blood albumin decreased
subjects affected / exposed	7 / 71 (9.86%)	2 / 16 (12.50%)	0 / 18 (0.00%)	2 / 21 (9.52%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	7	2	0	2	1	1
Blood alkaline phosphatase increased
subjects affected / exposed	10 / 71 (14.08%)	3 / 16 (18.75%)	1 / 18 (5.56%)	4 / 21 (19.05%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	10	3	1	4	0	1
Blood bicarbonate decreased
subjects affected / exposed	21 / 71 (29.58%)	1 / 16 (6.25%)	5 / 18 (27.78%)	6 / 21 (28.57%)	4 / 14 (28.57%)	4 / 12 (33.33%)
occurrences all number	21	1	5	6	4	4
Blood bilirubin increased
subjects affected / exposed	14 / 71 (19.72%)	5 / 16 (31.25%)	7 / 18 (38.89%)	1 / 21 (4.76%)	2 / 14 (14.29%)	1 / 12 (8.33%)
occurrences all number	14	5	7	1	2	1
Blood calcium decreased
subjects affected / exposed	5 / 71 (7.04%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	0	0	0	0	0
Blood calcium increased
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Blood cholesterol increased
subjects affected / exposed	12 / 71 (16.90%)	4 / 16 (25.00%)	6 / 18 (33.33%)	8 / 21 (38.10%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	12	4	6	8	1	0
Blood creatinine increased
subjects affected / exposed	9 / 71 (12.68%)	3 / 16 (18.75%)	1 / 18 (5.56%)	2 / 21 (9.52%)	2 / 14 (14.29%)	0 / 12 (0.00%)
occurrences all number	9	3	1	2	2	0
Blood glucose decreased
subjects affected / exposed	26 / 71 (36.62%)	6 / 16 (37.50%)	9 / 18 (50.00%)	7 / 21 (33.33%)	5 / 14 (35.71%)	1 / 12 (8.33%)
occurrences all number	26	6	9	7	5	1
Blood glucose increased
subjects affected / exposed	15 / 71 (21.13%)	5 / 16 (31.25%)	0 / 18 (0.00%)	2 / 21 (9.52%)	9 / 14 (64.29%)	3 / 12 (25.00%)
occurrences all number	15	5	0	2	9	3
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Blood lactic acid increased
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	0	0
Blood magnesium decreased
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0	0
Blood pH increased
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Blood phosphorus decreased
subjects affected / exposed	19 / 71 (26.76%)	2 / 16 (12.50%)	4 / 18 (22.22%)	1 / 21 (4.76%)	3 / 14 (21.43%)	1 / 12 (8.33%)
occurrences all number	19	2	4	1	3	1
Blood potassium decreased
subjects affected / exposed	15 / 71 (21.13%)	5 / 16 (31.25%)	1 / 18 (5.56%)	2 / 21 (9.52%)	4 / 14 (28.57%)	1 / 12 (8.33%)
occurrences all number	15	5	1	2	4	1
Blood potassium increased
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	4 / 21 (19.05%)	4 / 14 (28.57%)	8 / 12 (66.67%)
occurrences all number	0	1	0	4	4	8
Blood pressure decreased
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Blood pressure diastolic increased
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	1	0	0	0	2
Blood pressure increased
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	1	0
Blood pressure systolic increased
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Blood sodium decreased
subjects affected / exposed	27 / 71 (38.03%)	5 / 16 (31.25%)	6 / 18 (33.33%)	7 / 21 (33.33%)	4 / 14 (28.57%)	5 / 12 (41.67%)
occurrences all number	27	5	6	7	4	5
Blood sodium increased
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	1	0	0
Blood triglycerides increased
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Blood uric acid increased
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	1	0
Blood urine present
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Breath sounds abnormal
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	3 / 18 (16.67%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	3	0	0	0
Chlamydia test positive
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Electrocardiogram abnormal
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Haemoglobin decreased
subjects affected / exposed	7 / 71 (9.86%)	3 / 16 (18.75%)	1 / 18 (5.56%)	1 / 21 (4.76%)	3 / 14 (21.43%)	1 / 12 (8.33%)
occurrences all number	7	3	1	1	3	1
Helicobacter test positive
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Lipase increased
subjects affected / exposed	8 / 71 (11.27%)	3 / 16 (18.75%)	1 / 18 (5.56%)	1 / 21 (4.76%)	3 / 14 (21.43%)	2 / 12 (16.67%)
occurrences all number	8	3	1	1	3	2
Low density lipoprotein increased
subjects affected / exposed	10 / 71 (14.08%)	1 / 16 (6.25%)	4 / 18 (22.22%)	8 / 21 (38.10%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	10	1	4	8	0	0
Neutrophil count decreased
subjects affected / exposed	25 / 71 (35.21%)	7 / 16 (43.75%)	5 / 18 (27.78%)	11 / 21 (52.38%)	10 / 14 (71.43%)	2 / 12 (16.67%)
occurrences all number	25	7	5	11	10	2
Platelet count decreased
subjects affected / exposed	5 / 71 (7.04%)	1 / 16 (6.25%)	3 / 18 (16.67%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	5	1	3	1	1	0
Weight decreased
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	3 / 14 (21.43%)	1 / 12 (8.33%)
occurrences all number	4	0	0	1	3	1
White blood cell count decreased
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Arthropod bite
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	1	1
Clavicle fracture
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Contusion
subjects affected / exposed	2 / 71 (2.82%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	2 / 14 (14.29%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	2	0
Genital injury
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Hand fracture
subjects affected / exposed	5 / 71 (7.04%)	0 / 16 (0.00%)	2 / 18 (11.11%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	0	2	0	0	0
Laceration
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Ligament rupture
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Ligament sprain
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Lip injury
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Meniscus injury
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Post procedural swelling
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Post-traumatic pain
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Procedural pain
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Skin abrasion
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Stoma site rash
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Wrist fracture
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Congenital, familial and genetic disorders
Cerebral palsy
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Cardiac disorders
Atrioventricular block first degree
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Congestive cardiomyopathy
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Left ventricular hypertrophy
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Palpitations
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Sinus bradycardia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Tachycardia
subjects affected / exposed	5 / 71 (7.04%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	0	0	0	0	0
Nervous system disorders
Disturbance in attention
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Dizziness
subjects affected / exposed	9 / 71 (12.68%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	9	1	0	0	0	0
Dysarthria
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0	0
Dyscalculia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Dysgraphia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Dyslalia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Dyslexia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Epilepsy
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Facial paralysis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Facial paresis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Febrile convulsion
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Headache
subjects affected / exposed	29 / 71 (40.85%)	10 / 16 (62.50%)	4 / 18 (22.22%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	29	10	4	1	1	0
Hyperreflexia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Hypersomnia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Hypertonia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Hypoaesthesia
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0	0
Language disorder
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Meningeal disorder
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Migraine
subjects affected / exposed	2 / 71 (2.82%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0	0
Monoparesis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Muscle spasticity
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Neuropathy peripheral
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Paraesthesia
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Posterior reversible encephalopathy syndrome
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Psychomotor hyperactivity
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Seizure
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	4	0	0	0	1	1
Speech disorder
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Syncope
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0	0
Thrombotic stroke
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Unresponsive to stimuli
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Blood and lymphatic system disorders
Haemolytic anaemia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Immune thrombocytopenic purpura
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Iron deficiency anaemia
subjects affected / exposed	3 / 71 (4.23%)	1 / 16 (6.25%)	1 / 18 (5.56%)	1 / 21 (4.76%)	3 / 14 (21.43%)	1 / 12 (8.33%)
occurrences all number	3	1	1	1	3	1
Lymph node pain
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Lymphadenitis
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	2	0	0	1	1	0
Lymphadenopathy
subjects affected / exposed	12 / 71 (16.90%)	5 / 16 (31.25%)	2 / 18 (11.11%)	7 / 21 (33.33%)	4 / 14 (28.57%)	5 / 12 (41.67%)
occurrences all number	12	5	2	7	4	5
Neutropenia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Pancytopenia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Splenomegaly
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	1	0
Thrombocytopenia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Ear and labyrinth disorders
Cerumen impaction
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	1	0
Conductive deafness
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Deafness
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	1	0	0
Ear canal erythema
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Ear congestion
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	1	0	0	2
Ear discomfort
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	0	0
Ear pain
subjects affected / exposed	17 / 71 (23.94%)	0 / 16 (0.00%)	6 / 18 (33.33%)	4 / 21 (19.05%)	2 / 14 (14.29%)	0 / 12 (0.00%)
occurrences all number	17	0	6	4	2	0
Ear pruritus
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	2	0	0	1	1	0
Eustachian tube dysfunction
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Excessive cerumen production
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Hypoacusis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Middle ear effusion
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	1	0
Noninfective myringitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Otorrhoea
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	2 / 18 (11.11%)	3 / 21 (14.29%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	4	0	2	3	0	1
Tinnitus
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Tympanic membrane hyperaemia
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	2	0	1	0	1	0
Tympanosclerosis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Eye disorders
Conjunctival hyperaemia
subjects affected / exposed	1 / 71 (1.41%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0	0
Conjunctival pallor
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	2 / 14 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	2	0
Eye discharge
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	3 / 21 (14.29%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	4	0	0	3	1	0
Eye irritation
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Eye pain
subjects affected / exposed	5 / 71 (7.04%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	0	1	0	0	0
Eye pruritus
subjects affected / exposed	3 / 71 (4.23%)	2 / 16 (12.50%)	1 / 18 (5.56%)	2 / 21 (9.52%)	1 / 14 (7.14%)	2 / 12 (16.67%)
occurrences all number	3	2	1	2	1	2
Eye swelling
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	1	0	0	0
Eyelid oedema
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	1	0	0	1
Eyelid thickening
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Iris disorder
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Keratitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Lacrimation increased
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Ocular hyperaemia
subjects affected / exposed	8 / 71 (11.27%)	1 / 16 (6.25%)	3 / 18 (16.67%)	2 / 21 (9.52%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	8	1	3	2	1	1
Periorbital oedema
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	1	0
Photophobia
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Vision blurred
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Visual impairment
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Abdominal distension
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	2	0	0	1	0	1
Abdominal hernia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Abdominal pain
subjects affected / exposed	20 / 71 (28.17%)	5 / 16 (31.25%)	3 / 18 (16.67%)	2 / 21 (9.52%)	3 / 14 (21.43%)	0 / 12 (0.00%)
occurrences all number	20	5	3	2	3	0
Abdominal pain lower
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	1	0
Abdominal pain upper
subjects affected / exposed	9 / 71 (12.68%)	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	9	1	1	0	0	0
Abdominal tenderness
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0	0
Anal pruritus
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Anorectal discomfort
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Aphthous ulcer
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0	0
Breath odour
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	2 / 18 (11.11%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	2	0	0	0
Cheilitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Colitis
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Constipation
subjects affected / exposed	5 / 71 (7.04%)	0 / 16 (0.00%)	1 / 18 (5.56%)	1 / 21 (4.76%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	5	0	1	1	0	1
Dental caries
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	1	0
Diarrhoea
subjects affected / exposed	22 / 71 (30.99%)	2 / 16 (12.50%)	6 / 18 (33.33%)	8 / 21 (38.10%)	9 / 14 (64.29%)	7 / 12 (58.33%)
occurrences all number	22	2	6	8	9	7
Dyspepsia
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Dysphagia
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Flatulence
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	2	0	0	1	1	1
Food poisoning
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Gastritis
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0	0
Gingival erythema
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Gingival pain
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Infantile spitting up
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Infantile vomiting
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Inflammatory bowel disease
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Lip discolouration
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Lip ulceration
subjects affected / exposed	2 / 71 (2.82%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0	0
Mouth ulceration
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	1 / 18 (5.56%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	3	0	1	1	1	0
Nausea
subjects affected / exposed	23 / 71 (32.39%)	5 / 16 (31.25%)	5 / 18 (27.78%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	23	5	5	1	1	0
Noninfective gingivitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Oesophagitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Oral discharge
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Oral disorder
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	2 / 21 (9.52%)	1 / 14 (7.14%)	2 / 12 (16.67%)
occurrences all number	2	0	0	2	1	2
Oral mucosal blistering
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Oral mucosal erythema
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Parotid gland enlargement
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Rectal haemorrhage
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	2 / 14 (14.29%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	2	0
Toothache
subjects affected / exposed	6 / 71 (8.45%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	6	1	0	0	0	0
Vomiting
subjects affected / exposed	26 / 71 (36.62%)	6 / 16 (37.50%)	8 / 18 (44.44%)	9 / 21 (42.86%)	6 / 14 (42.86%)	3 / 12 (25.00%)
occurrences all number	26	6	8	9	6	3
Hepatobiliary disorders
Hepatic steatosis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	0	0
Hepatomegaly
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	3 / 21 (14.29%)	2 / 14 (14.29%)	0 / 12 (0.00%)
occurrences all number	2	0	0	3	2	0
Hyperbilirubinaemia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Ocular icterus
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	1	0
Skin and subcutaneous tissue disorders
Acanthosis nigricans
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0	0
Acne
subjects affected / exposed	9 / 71 (12.68%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	9	1	0	0	0	0
Alopecia
subjects affected / exposed	1 / 71 (1.41%)	2 / 16 (12.50%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0	0
Blister
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	2	0	0	1	1	0
Dermatitis allergic
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	2 / 18 (11.11%)	0 / 21 (0.00%)	3 / 14 (21.43%)	1 / 12 (8.33%)
occurrences all number	4	0	2	0	3	1
Dermatitis atopic
subjects affected / exposed	4 / 71 (5.63%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	2 / 14 (14.29%)	1 / 12 (8.33%)
occurrences all number	4	1	0	0	2	1
Dermatitis diaper
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	1	2
Drug eruption
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0	0
Dry skin
subjects affected / exposed	2 / 71 (2.82%)	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 21 (0.00%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	2	1	1	0	1	1
Dyshidrotic eczema
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Eczema
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	2 / 18 (11.11%)	1 / 21 (4.76%)	2 / 14 (14.29%)	1 / 12 (8.33%)
occurrences all number	3	0	2	1	2	1
Erythema
subjects affected / exposed	9 / 71 (12.68%)	2 / 16 (12.50%)	2 / 18 (11.11%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	9	2	2	1	1	0
Hyperhidrosis
subjects affected / exposed	2 / 71 (2.82%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0	0
Macule
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	4 / 21 (19.05%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	4	0	0
Nail discolouration
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Night sweats
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	0	0
Pain of skin
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Papule
subjects affected / exposed	7 / 71 (9.86%)	2 / 16 (12.50%)	0 / 18 (0.00%)	3 / 21 (14.29%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	7	2	0	3	1	0
Petechiae
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Photosensitivity reaction
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Pityriasis alba
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	2 / 21 (9.52%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	2	0	0
Pityriasis rosea
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Pruritus
subjects affected / exposed	12 / 71 (16.90%)	3 / 16 (18.75%)	2 / 18 (11.11%)	2 / 21 (9.52%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	12	3	2	2	1	1
Pruritus generalised
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	1	0	0	0
Rash
subjects affected / exposed	8 / 71 (11.27%)	6 / 16 (37.50%)	2 / 18 (11.11%)	6 / 21 (28.57%)	7 / 14 (50.00%)	9 / 12 (75.00%)
occurrences all number	8	6	2	6	7	9
Rash generalised
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	3 / 18 (16.67%)	0 / 21 (0.00%)	2 / 14 (14.29%)	3 / 12 (25.00%)
occurrences all number	4	0	3	0	2	3
Rash macular
subjects affected / exposed	2 / 71 (2.82%)	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	1	0	0	0
Rash maculo-papular
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Rash papular
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	2	0	1	0	1	1
Scab
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	0	0
Seborrhoeic dermatitis
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	2	0	0	1	0	1
Skin discolouration
subjects affected / exposed	2 / 71 (2.82%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0	0
Skin exfoliation
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Skin hyperpigmentation
subjects affected / exposed	1 / 71 (1.41%)	2 / 16 (12.50%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	1	0	0
Skin hypopigmentation
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Skin lesion
subjects affected / exposed	7 / 71 (9.86%)	3 / 16 (18.75%)	0 / 18 (0.00%)	3 / 21 (14.29%)	1 / 14 (7.14%)	2 / 12 (16.67%)
occurrences all number	7	3	0	3	1	2
Skin plaque
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	3 / 21 (14.29%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	3	0	0
Skin ulcer
subjects affected / exposed	1 / 71 (1.41%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0	0
Swelling face
subjects affected / exposed	5 / 71 (7.04%)	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	1	1	0	0	0
Trichorrhexis
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Urticaria
subjects affected / exposed	3 / 71 (4.23%)	1 / 16 (6.25%)	1 / 18 (5.56%)	2 / 21 (9.52%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	1	1	2	0	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Dysuria
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	1	0
Haematuria
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0	0
Kidney enlargement
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Micturition urgency
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Pollakiuria
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	1	0	0
Proteinuria
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Tubulointerstitial nephritis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Urine odour abnormal
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	10 / 71 (14.08%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	10	0	0	0	0	0
Back pain
subjects affected / exposed	16 / 71 (22.54%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	16	1	0	0	0	0
Costochondritis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Facial asymmetry
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Flank pain
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0	0
Groin pain
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Head deformity
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Joint effusion
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Joint stiffness
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Joint swelling
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0	0
Kyphosis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Limb discomfort
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Muscle spasms
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	1 / 18 (5.56%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	4	0	1	1	1	0
Muscle twitching
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Musculoskeletal discomfort
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0	0
Myalgia
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Neck pain
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0	0
Pain in extremity
subjects affected / exposed	10 / 71 (14.08%)	3 / 16 (18.75%)	3 / 18 (16.67%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	10	3	3	0	1	0
Pain in jaw
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Pathological fracture
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Spinal pain
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Infections and infestations
Abscess limb
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	1	0	0
Acarodermatitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	1	0
Acute sinusitis
subjects affected / exposed	5 / 71 (7.04%)	1 / 16 (6.25%)	1 / 18 (5.56%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	1	1	1	0	0
Bacterial sepsis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Bacterial vaginosis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Body tinea
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	2 / 14 (14.29%)	3 / 12 (25.00%)
occurrences all number	2	0	0	1	2	3
Breast abscess
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Bronchiolitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	0	0	0	1	1	1
Bronchitis
subjects affected / exposed	4 / 71 (5.63%)	2 / 16 (12.50%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	4	2	0	1	1	1
Bronchitis viral
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Candida infection
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Cellulitis
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	1	0	0
Cervicitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Cervicitis human papilloma virus
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Cervicitis trichomonal
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Chlamydial cervicitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Chronic sinusitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Clostridium difficile colitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	4 / 71 (5.63%)	3 / 16 (18.75%)	3 / 18 (16.67%)	4 / 21 (19.05%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	4	3	3	4	1	0
Conjunctivitis bacterial
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Coxsackie viral infection
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Dermatophytosis of nail
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Dysentery
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Epididymitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Escherichia urinary tract infection
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	2	0	0	1	1	1
Fungal skin infection
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	2 / 18 (11.11%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	2	0	0	0
Gastroenteritis
subjects affected / exposed	5 / 71 (7.04%)	0 / 16 (0.00%)	4 / 18 (22.22%)	6 / 21 (28.57%)	7 / 14 (50.00%)	3 / 12 (25.00%)
occurrences all number	5	0	4	6	7	3
Gastroenteritis rotavirus
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Gingivitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
H1N1 influenza
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
HIV associated nephropathy
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
HIV wasting syndrome
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	1	0	0	0	0	1
Hand-foot-and-mouth disease
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Herpes simplex
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Herpes zoster
subjects affected / exposed	5 / 71 (7.04%)	1 / 16 (6.25%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	1	0	1	0	0
Hymenolepiasis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Impetigo
subjects affected / exposed	0 / 71 (0.00%)	2 / 16 (12.50%)	0 / 18 (0.00%)	9 / 21 (42.86%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	0	2	0	9	1	1
Infection parasitic
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Influenza
subjects affected / exposed	2 / 71 (2.82%)	2 / 16 (12.50%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	0	0	0	0
Laryngitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Latent tuberculosis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	0	0
Lice infestation
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	2 / 21 (9.52%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	2	0	0
Meningitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Molluscum contagiosum
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	2 / 18 (11.11%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	2	1	0	0
Mycobacterium avium complex infection
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Mycoplasma infection
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Oesophageal candidiasis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Onychomycosis
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	1	0	0	0
Oral candidiasis
subjects affected / exposed	7 / 71 (9.86%)	0 / 16 (0.00%)	0 / 18 (0.00%)	2 / 21 (9.52%)	2 / 14 (14.29%)	1 / 12 (8.33%)
occurrences all number	7	0	0	2	2	1
Oral hairy leukoplakia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Oral herpes
subjects affected / exposed	1 / 71 (1.41%)	1 / 16 (6.25%)	2 / 18 (11.11%)	3 / 21 (14.29%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	1	1	2	3	1	0
Orchitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Oropharyngeal candidiasis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Oropharyngeal gonococcal infection
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Otitis externa
subjects affected / exposed	5 / 71 (7.04%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	0	1	0	0	0
Otitis media
subjects affected / exposed	10 / 71 (14.08%)	2 / 16 (12.50%)	4 / 18 (22.22%)	9 / 21 (42.86%)	4 / 14 (28.57%)	2 / 12 (16.67%)
occurrences all number	10	2	4	9	4	2
Otitis media acute
subjects affected / exposed	4 / 71 (5.63%)	1 / 16 (6.25%)	1 / 18 (5.56%)	1 / 21 (4.76%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	4	1	1	1	1	0
Otitis media chronic
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Pancreatitis viral
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Parotitis
subjects affected / exposed	1 / 71 (1.41%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0	0
Persistent generalised lymphadenopathy
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	0	0	0	1	1	1
Pharyngeal chlamydia infection
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Pharyngitis
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	3 / 18 (16.67%)	2 / 21 (9.52%)	6 / 14 (42.86%)	4 / 12 (33.33%)
occurrences all number	4	0	3	2	6	4
Pharyngitis streptococcal
subjects affected / exposed	3 / 71 (4.23%)	2 / 16 (12.50%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	2	0	0	0	0
Pneumocystis jirovecii pneumonia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Pneumonia
subjects affected / exposed	3 / 71 (4.23%)	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 21 (0.00%)	2 / 14 (14.29%)	1 / 12 (8.33%)
occurrences all number	3	1	1	0	2	1
Pneumonia bacterial
subjects affected / exposed	4 / 71 (5.63%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	4	1	0	0	1	0
Proctitis chlamydial
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Proctitis gonococcal
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Pulmonary tuberculosis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Purulent discharge
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	2 / 21 (9.52%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	2	0	0
Rash pustular
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Rhinitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	2 / 21 (9.52%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	2	1	0
Rubella
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1
Sialoadenitis
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	1	0	0
Sinusitis bacterial
subjects affected / exposed	2 / 71 (2.82%)	3 / 16 (18.75%)	3 / 18 (16.67%)	5 / 21 (23.81%)	2 / 14 (14.29%)	0 / 12 (0.00%)
occurrences all number	2	3	3	5	2	0
Skin candida
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	2 / 21 (9.52%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	0	0	0	2	1	1
Skin infection
subjects affected / exposed	1 / 71 (1.41%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0	0
Staphylococcal abscess
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Subcutaneous abscess
subjects affected / exposed	0 / 71 (0.00%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0
Tinea capitis
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	1 / 18 (5.56%)	4 / 21 (19.05%)	2 / 14 (14.29%)	2 / 12 (16.67%)
occurrences all number	1	0	1	4	2	2
Tinea faciei
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	2 / 14 (14.29%)	0 / 12 (0.00%)
occurrences all number	1	0	0	1	2	0
Tinea infection
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	2 / 21 (9.52%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	2	0	0	2	1	0
Tinea pedis
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0	0
Tinea versicolour
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Tonsillitis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	3 / 21 (14.29%)	3 / 14 (21.43%)	1 / 12 (8.33%)
occurrences all number	0	0	0	3	3	1
Tooth abscess
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	1 / 71 (1.41%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	1	1	0	0	0	1
Urethritis chlamydial
subjects affected / exposed	4 / 71 (5.63%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0	0
Urethritis gonococcal
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Urinary tract infection bacterial
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	2	0	1	0	0	1
Urinary tract infection staphylococcal
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Vaginitis chlamydial
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Varicella
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	2 / 18 (11.11%)	0 / 21 (0.00%)	0 / 14 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	2	0	0	1
Vulvovaginal candidiasis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Vulvovaginitis
subjects affected / exposed	2 / 71 (2.82%)	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	1	0
Vulvovaginitis gonococcal
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Metabolism and nutrition disorders
Body fat disorder
subjects affected / exposed	3 / 71 (4.23%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0	0
Decreased appetite
subjects affected / exposed	9 / 71 (12.68%)	1 / 16 (6.25%)	3 / 18 (16.67%)	3 / 21 (14.29%)	4 / 14 (28.57%)	3 / 12 (25.00%)
occurrences all number	9	1	3	3	4	3
Dehydration
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	1 / 12 (8.33%)
occurrences all number	1	0	0	0	1	1
Failure to thrive
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	3 / 14 (21.43%)	3 / 12 (25.00%)
occurrences all number	0	0	0	1	3	3
Hyperlactacidaemia
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Hyperlipidaemia
subjects affected / exposed	2 / 71 (2.82%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	1	0	0
Hypertriglyceridaemia
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Lactic acidosis
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 21 (4.76%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0
Malnutrition
subjects affected / exposed	0 / 71 (0.00%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	1 / 14 (7.14%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0
Metabolic syndrome
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Obesity
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0
Type 2 diabetes mellitus
subjects affected / exposed	1 / 71 (1.41%)	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 21 (0.00%)	0 / 14 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

11 Jun 2008

Amendment 1: Added references to a third potential formulation (in development), to be studied in Cohort IV (≥6 months to <2 years) and Cohort V (≥4 weeks to <6 months); added information on 5 year follow-up of participants both on-drug and off-drug including schedules of evaluations; updated inclusion and exclusion criteria.

09 Apr 2010

Amendment 2: Increased total study sample size to 160 participants; specified that the raltegravir formulation to be evaluated in participants ≥4 weeks to <2 years of age was the oral granules for suspension, and added specific dosing instruction, updated inclusion and exclusion criteria, and added a dried blood spot assay.

Were there any global interruptions to the trial? No

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

None reported

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Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with one or more adverse events (AEs)

Primary: Number of participants with one or more adverse events (AEs)

Primary: Number of participants who discontinued study medication due to an AE

Primary: Number of participants who discontinued study medication due to an AE

Primary: Area under the concentration-time curve from time 0-12 hours post-dose for plasma raltegravir (AUC0-12h)

Primary: Area under the concentration-time curve from time 0-12 hours post-dose for plasma raltegravir (AUC0-12h)

Primary: Maximum concentration of plasma raltegravir (Cmax)

Primary: Maximum concentration of plasma raltegravir (Cmax)

Primary: Time to maximum concentration of plasma raltegravir (Tmax)

Primary: Time to maximum concentration of plasma raltegravir (Tmax)

Primary: Concentration at 12 hours post-dose of plasma raltegravir (C12hr)

Primary: Concentration at 12 hours post-dose of plasma raltegravir (C12hr)

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Substantial protocol amendments (globally)

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