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Clinical Trial Results:
A Multicenter, Long-term, Open-label Study to Evaluate the Safety of MT10109L (NivobotulinumtoxinA) for the Treatment of Glabellar Lines and Lateral Canthal Lines

Summary
EudraCT number	2014-005303-24
Trial protocol	DE BE
Global end of trial date	16 Feb 2023

Results information
Results version number	v1(current)
This version publication date	25 Sep 2024
First version publication date	25 Sep 2024
Other versions
Summary report(s)	Supplementary Results for Efficacy Endpoints

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

MT10109L-004

ISRCTN number

US NCT number

NCT04157686

WHO universal trial number (UTN)

Other trial identifiers

IND: 121473

Sponsor organisation name

Medytox Inc

Sponsor organisation address

78, Gangni 1-gil, Ochang-eup, Cheongwon-gu, Cheongju-si, Korea, Republic of, 28196

Public contact

Wansoon Lee, Medytox, +82 269015851, drlee@medytox.com

Scientific contact

Wansoon Lee, Medytox, +82 269015851, drlee@medytox.com

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

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?

Analysis stage

Final

Date of interim/final analysis

09 May 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

16 Feb 2023

Global end of trial reached?

Yes

Global end of trial date

16 Feb 2023

Was the trial ended prematurely?

Main objective of the trial

To evaluate the long-term safety of repeat treatments of MT10109L in participants with moderate to severe GL, LCL, or both (GL and LCL). This was a Phase 3, multicenter, open-label, repeat treatment extension study to evaluate the long-term safety of MT10109L in treating Glabellar Lines (GL), Lateral Canthal Lines (LCL), or both (GL and LCL) conducted across 40 global study centers. All participants who completed studies MT10109L-001 (GL; EudraCT Number: 2018-004384-31), MT10109L-002 (LCL; EudraCT Number: 2014-005279-10), MT10109L-005 (GL with or without LCL; EudraCT Number: 2014-005301-21), and MT10109L-006 (LCL with or without GL; EudraCT Number: 2014-005302-38) were eligible to enroll into this study. Given the objective of this study was long-term safety, we present the safety-related endpoint data within the full data set. Additionally, we have attached a summary of conclusions page for the efficacy endpoints.

Protection of trial subjects

The study protocol, all study protocol amendments, written study participant information, informed consent form (ICF), Investigator’s Brochure (IB) and any other relevant documents were reviewed and approved by an independent ethics committee (IEC) or institutional review board (IRB) at each study center. The study was conducted in accordance with the protocol, the ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable International Council for Harmonization (ICH)/Good Clinical Practice (GCP) and other Guidelines, and applicable laws and regulations. An ICF approved by each study center’s IEC/IRB was signed by the participant or their legally authorized representative and the authorized person obtaining the ICF before the participant was entered in the study.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Oct 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 628

Country: Number of subjects enrolled

Canada: 126

Country: Number of subjects enrolled

Russian Federation: 42

Country: Number of subjects enrolled

United Kingdom: 56

Country: Number of subjects enrolled

Belgium: 22

Country: Number of subjects enrolled

Germany: 83

Worldwide total number of subjects

957

EEA total number of subjects

105

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)

902

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Approximately 800 participants were planned to be enrolled. A total of 957 participants were enrolled and treated, and 759 participants completed the study. There were 794 participants in the modified intent-to-treat (mITT) population, which were used for the efficacy of EU agencies and 957 pts in ITT population which were used for safety analyze.

Screening details

Study MT10109L-004 is an open-label extension involving participants from MT10109L-001, -002, -005 and -006 (referred to as Lead-In studies).Participants from the lead-in studies, who met the eligibility criteria, were enrolled to continue receiving additional cycles of MT10109L in their respective treatment areas:

Period 1 title

Overall period

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo/MT10109L 20U

Arm description

The participant pool in this arm were from the MT 10109L-001 lead in study (EudraCT Number: 2018-004384-31) who received placebo in period 1 and MT 10109L 20U in period 2. Eligible participants from this study continued receiving 20 U Dose in this open label MT 10109L-004 study.

Arm type

Experimental

Investigational medicinal product name

MT 10109L

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection, Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

MT10109L 20 U was injected into the GL area.

Placebo/MT10109L 24U

Arm description

The participant pool in this arm were from the MT10109L-002 lead-in study (EudraCT Number: 2014-005279-10), who received Placebo in period 1 and MT10109L 24U in period 2. Eligible participants from this study continued receiving 24 U Dose in the open-label MT10109L-004 study. MT10109L 24 U werel injected into the LCL area.

Arm type

Experimental

Investigational medicinal product name

MT10109L

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection, Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

MT10109L 24 U was injected into the LCL area.

Placebo/MT10109L 44U

Arm description

The participant pool in this arm were from the MT10109L-005 (EudraCT Number: 2014-005301-21) and MT10109L-006 (EudraCT Number: 2014-005302-38) lead-in studies, who received Placebo in periods 1 & 2. Eligible participants from this study received 20U Dose into the GL area and 24 U Dose into the LCL area in the open-label MT10109L-004 study. MT10109L 20U was injected into the GL area plus MT10109L 24U injected into the LCL area.

Arm type

Experimental

Investigational medicinal product name

MT10109L

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection, Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

MT10109L 20 U was injected into the GL area plus MT10109L 24 U was injected into the LCL area

MT10109L 20 U / MT10109L 20 U

Arm description

The participant pool in this arm were from the MT10109L-001 lead-in study (EudraCT Number: 2018-004384-31), who received MT10109L 20U each in period 1 and period 2. Eligible participants from this study continued receiving Dose 1 in the open-label MT10109L-004 study. MT10109L Dose 1: MT10109L 20U was injected into the GL area.

Arm type

Experimental

Investigational medicinal product name

MT10109L

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection, Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

MT10109L 20 U was injected into the GL area.

MT10109L 24U/MT10109L 24U

Arm description

The participant pool in this arm were from the MT10109L-002 lead-in study (EudraCT Number: 2014-005279-10), who received MT10109L 24U each in period 1 and period 2. Eligible participants from this study continued receiving 24U dose in this open-label MT10109L-004 study. MT10109L 24 U were injected into the LCL area

Arm type

Experimental

Investigational medicinal product name

MT10109L

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection, Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

MT10109L 24 U was injected into the LCL area.

MT10109L 20U/MT10109L 44U

Arm description

The participant pool in this arm were from the from MT10109L-005 lead-in study (EudraCT Number: 2014-005301-21), who received MT10109L 20U in periods 1 and 2. Eligible participants from this study received 20U dose into the GL area and 24U dose into the LCL area in the open-label MT10109L-004 study. MT10109L 20U were injected into the GL area plus MT10109L 24U were injected into the LCL area.

Arm type

Experimental

Investigational medicinal product name

MT10109L

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection, Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

MT10109L 20U was injected into the GL area plus MT10109L 24U injected into the LCL area.

MT10109L 24U/MT10109L 44U

Arm description

The participant pool in this arm were from the MT10109L-006 lead-in study (EudraCT Number: 2014-005302-38), who received MT10109L 24U in periods 1 and 2. Eligible participants from this study receives 20 U dose into the GL area and 24 U dose into the LCL area in the open-label MT10109L-004 study. MT10109L 20 U were injected into the GL area plus MT10109L 24 U dose injected into the LCL area.

Arm type

Experimental

Investigational medicinal product name

MT10109L

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection, Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

MT10109L 20 U was injected into the GL area plus MT10109L 24 U was injected into the LCL area.

MT10109L 44U /MT10109L 44U

Arm description

The participant pool in this arm were from the MT10109L-005 (EudraCT Number: 2014-005301-21) and MT10109L-006 (EudraCT Number: 2014-005302-38) lead-in studies, who received MT10109L 20 U into GL and 24U into LCL in periods 1 & 2. Eligible participants from this study received 20 U Dose into the GL area and 24 U Dose into the LCL area in this open-label MT10109L-004 study. MT10109L 20 U were injected into the GL area plus MT10109L 24 U injected into the LCL area.

Arm type

Experimental

Investigational medicinal product name

MT10109L

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection, Sterile concentrate

Routes of administration

Intramuscular use

Dosage and administration details

MT10109L 20 U was injected into the GL area plus MT10109L 24 U was injected into the LCL area.

Number of subjects in period 1	Placebo/MT10109L 20U	Placebo/MT10109L 24U	Placebo/MT10109L 44U	MT10109L 20 U / MT10109L 20 U	MT10109L 24U/MT10109L 24U	MT10109L 20U/MT10109L 44U	MT10109L 24U/MT10109L 44U	MT10109L 44U /MT10109L 44U
Started	55	56	118	116	108	128	123	253
Completed	43	41	89	87	83	106	92	218
Not completed	12	15	29	29	25	22	31	35
Adverse event, serious fatal	-	-	-	2	-	-	-	-
Consent withdrawn by subject	10	10	12	20	12	11	18	24
Physician decision	-	-	1	-	1	-	3	-
Adverse event, non-fatal	1	-	1	-	1	-	-	-
Pregnancy	-	1	3	-	-	-	3	-
Other reasons	-	2	4	1	4	6	-	1
Lost to follow-up	1	2	8	6	6	3	7	9
Protocol deviation	-	-	-	-	1	-	-	-
Lack of efficacy	-	-	-	-	-	2	-	1

Baseline characteristics

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Reporting group title

Placebo/MT10109L 20U

Reporting group description

Reporting group title

Placebo/MT10109L 24U

Reporting group description

Reporting group title

Placebo/MT10109L 44U

Reporting group description

Reporting group title

MT10109L 20 U / MT10109L 20 U

Reporting group description

Reporting group title

MT10109L 24U/MT10109L 24U

Reporting group description

Reporting group title

MT10109L 20U/MT10109L 44U

Reporting group description

Reporting group title

MT10109L 24U/MT10109L 44U

Reporting group description

Reporting group title

MT10109L 44U /MT10109L 44U

Reporting group description

The participant pool in this arm were from the MT10109L-005 (EudraCT Number: 2014-005301-21) and MT10109L-006 (EudraCT Number: 2014-005302-38) lead-in studies, who received MT10109L 20 U into GL and 24U into LCL in periods 1 & 2. Eligible participants from this study received 20 U Dose into the GL area and 24 U Dose into the LCL area in this open-label MT10109L-004 study. MT10109L 20 U were injected into the GL area plus MT10109L 24 U injected into the LCL area.

Reporting group values	Placebo/MT10109L 20U	Placebo/MT10109L 24U	Placebo/MT10109L 44U	MT10109L 20 U / MT10109L 20 U	MT10109L 24U/MT10109L 24U	MT10109L 20U/MT10109L 44U	MT10109L 24U/MT10109L 44U	MT10109L 44U /MT10109L 44U	Total
Number of subjects	55	56	118	116	108	128	123	253	957
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	54	54	110	107	103	120	113	241	902
From 65-84 years	1	2	7	9	5	7	10	12	53
85 years and over	0	0	1	0	0	1	0	0	2
Age continuous
Units: years
arithmetic mean (standard deviation)	47.1 ( 10.18 )	46.7 ( 11.75 )	48.2 ( 11.68 )	46.9 ( 12.17 )	47.1 ( 10.34 )	47.8 ( 11.24 )	48.5 ( 10.53 )	47.9 ( 10.80 )	-
Gender categorical
Units: Subjects
Female	53	42	99	106	87	109	103	227	826
Male	2	14	19	10	21	19	20	26	131

Subject analysis set title

Demographic and other Baseline Characteristics - ITT

Subject analysis set type

Intention-to-treat

Subject analysis set description

Participants from prior Phase 3 studies were enrolled in this study as follows: 171 participants from -001 study, 164 participants from -002 study, 303 participants from -005 study, and 319 participants from -006 study; thus, consisting of 957 participants in the ITT analysis set.

Subject analysis set title

Demographic and other Baseline Characteristics -mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Participants from prior Phase 3 study were enrolled in this study as follows: 142 participants from 001 study, 127 participants from 002 study, 255 participants from 005 study, and 270 participants from 006 study; thus, consisting of 794 participants in the mITT analysis set.

Subject analysis sets values	Demographic and other Baseline Characteristics - ITT	Demographic and other Baseline Characteristics -mITT
Number of subjects	957	794
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	902	746
From 65-84 years	53	46
85 years and over	2	2
Age continuous
Units: years
arithmetic mean (standard deviation)	47.7 ( 11.06 )	48.6 ( 10.65 )
Gender categorical
Units: Subjects
Female	826	705
Male	131	89

End points

Top of page

Reporting group title

Placebo/MT10109L 20U

Reporting group description

Reporting group title

Placebo/MT10109L 24U

Reporting group description

Reporting group title

Placebo/MT10109L 44U

Reporting group description

Reporting group title

MT10109L 20 U / MT10109L 20 U

Reporting group description

Reporting group title

MT10109L 24U/MT10109L 24U

Reporting group description

Reporting group title

MT10109L 20U/MT10109L 44U

Reporting group description

Reporting group title

MT10109L 24U/MT10109L 44U

Reporting group description

Reporting group title

MT10109L 44U /MT10109L 44U

Reporting group description

The participant pool in this arm were from the MT10109L-005 (EudraCT Number: 2014-005301-21) and MT10109L-006 (EudraCT Number: 2014-005302-38) lead-in studies, who received MT10109L 20 U into GL and 24U into LCL in periods 1 & 2. Eligible participants from this study received 20 U Dose into the GL area and 24 U Dose into the LCL area in this open-label MT10109L-004 study. MT10109L 20 U were injected into the GL area plus MT10109L 24 U injected into the LCL area.

Subject analysis set title

Demographic and other Baseline Characteristics - ITT

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Demographic and other Baseline Characteristics -mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Primary: Number of Participants Who Experienced Any Adverse Event (AE)

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End point title

Number of Participants Who Experienced Any Adverse Event (AE) ^[1]

End point description

End point type

Primary

End point timeframe

Baseline to Day 720 or Study Exit

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: Data has only been summarized as frequency of events per arm. No statistical comparisons were made between the arms.

End point values	Placebo/MT10109L 20U	Placebo/MT10109L 24U	Placebo/MT10109L 44U	MT10109L 20 U / MT10109L 20 U	MT10109L 24U/MT10109L 24U	MT10109L 20U/MT10109L 44U	MT10109L 24U/MT10109L 44U	MT10109L 44U /MT10109L 44U
Number of subjects analysed	55	56	118	116	108	128	123	253
Units: number of participants	39	39	80	89	74	80	89	183

No statistical analyses for this end point

Primary: Number of Participants Who Experienced Treatment-Related Adverse Events (TEAEs)

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End point title

Number of Participants Who Experienced Treatment-Related Adverse Events (TEAEs) ^[2]

End point description

End point type

Primary

End point timeframe

Baseline to Day 720 or Study exit

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: Data has only been summarized as frequency of events per arm. No statistical comparisons were made between the arms.

End point values	Placebo/MT10109L 20U	Placebo/MT10109L 24U	Placebo/MT10109L 44U	MT10109L 20 U / MT10109L 20 U	MT10109L 24U/MT10109L 24U	MT10109L 20U/MT10109L 44U	MT10109L 24U/MT10109L 44U	MT10109L 44U /MT10109L 44U
Number of subjects analysed	55	56	118	116	108	128	123	253
Units: Number of Participants	18	4	31	34	11	22	42	73

No statistical analyses for this end point

Primary: Mean Change From Baseline in Pulse Rate (Beats Per Minute)

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End point title

Mean Change From Baseline in Pulse Rate (Beats Per Minute) ^[3]

End point description

End point type

Primary

End point timeframe

Baseline to Day 720 or Study Exit

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: Only descriptive statistics were used to summarize the mean changes from vital signs from baseline. No statistical comparisons were made between arms.

End point values	Placebo/MT10109L 20U	Placebo/MT10109L 24U	Placebo/MT10109L 44U	MT10109L 20 U / MT10109L 20 U	MT10109L 24U/MT10109L 24U	MT10109L 20U/MT10109L 44U	MT10109L 24U/MT10109L 44U	MT10109L 44U /MT10109L 44U
Number of subjects analysed	27	40	63	58	61	78	74	157
Units: beats/min
arithmetic mean (standard deviation)	3.2 ( 15.01 )	-2.2 ( 13.35 )	-1.2 ( 10.95 )	2.0 ( 12.77 )	0.6 ( 11.58 )	0.7 ( 10.97 )	3.0 ( 10.34 )	1.0 ( 8.93 )

No statistical analyses for this end point

Primary: Mean Change From Baseline in Systolic Blood Pressure (mm Hg)

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End point title

Mean Change From Baseline in Systolic Blood Pressure (mm Hg) ^[4]

End point description

End point type

Primary

End point timeframe

Baseline to Day 720 or Study Exit

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: Only descriptive statistics were used to summarize the mean changes from vital signs from baseline. No statistical comparisons were made between arms.

End point values	Placebo/MT10109L 20U	Placebo/MT10109L 24U	Placebo/MT10109L 44U	MT10109L 20 U / MT10109L 20 U	MT10109L 24U/MT10109L 24U	MT10109L 20U/MT10109L 44U	MT10109L 24U/MT10109L 44U	MT10109L 44U /MT10109L 44U
Number of subjects analysed	27	40	63	58	61	78	74	157
Units: mm Hg
arithmetic mean (standard deviation)	1.4 ( 12.59 )	-1.9 ( 10.44 )	1.9 ( 14.44 )	0.6 ( 16.72 )	1.1 ( 13.84 )	1.8 ( 15.24 )	1.4 ( 14.17 )	-0.4 ( 13.83 )

No statistical analyses for this end point

Primary: Mean Change From Baseline in Diastolic Blood Pressure (mm Hg)

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End point title

Mean Change From Baseline in Diastolic Blood Pressure (mm Hg) ^[5]

End point description

End point type

Primary

End point timeframe

Baseline to Day 720 or Study Exit

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: Only descriptive statistics were used to summarize the mean changes from vital signs from baseline. No statistical comparisons were made between arms.

End point values	Placebo/MT10109L 20U	Placebo/MT10109L 24U	Placebo/MT10109L 44U	MT10109L 20 U / MT10109L 20 U	MT10109L 24U/MT10109L 24U	MT10109L 20U/MT10109L 44U	MT10109L 24U/MT10109L 44U	MT10109L 44U /MT10109L 44U
Number of subjects analysed	27	40	63	58	61	78	74	157
Units: mm Hg
arithmetic mean (standard deviation)	1.1 ( 11.3 )	-0.6 ( 11.74 )	1.3 ( 9.61 )	1.5 ( 11.68 )	0.7 ( 7.57 )	0.0 ( 10.62 )	2.3 ( 9.53 )	-0.3 ( 9.46 )

No statistical analyses for this end point

Primary: Mean Change From Baseline in Respiratory Rate (Breaths Per Minute)

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End point title

Mean Change From Baseline in Respiratory Rate (Breaths Per Minute) ^[6]

End point description

End point type

Primary

End point timeframe

Baseline to Day 720 or Study Exit

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: Only descriptive statistics were used to summarize the mean changes from vital signs from baseline. No statistical comparisons were made between arms.

End point values	Placebo/MT10109L 20U	Placebo/MT10109L 24U	Placebo/MT10109L 44U	MT10109L 20 U / MT10109L 20 U	MT10109L 24U/MT10109L 24U	MT10109L 20U/MT10109L 44U	MT10109L 24U/MT10109L 44U	MT10109L 44U /MT10109L 44U
Number of subjects analysed	27	40	63	58	61	78	74	157
Units: breath/min
arithmetic mean (standard deviation)	0.3 ( 2.09 )	0.6 ( 2.15 )	-0.5 ( 1.92 )	0.2 ( 2.78 )	0.5 ( 1.94 )	-0.4 ( 2.29 )	0.4 ( 2.21 )	-0.1 ( 2.3 )

No statistical analyses for this end point

Primary: Number of Participants With Binding and Neutralizing Antibodies

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End point title

Number of Participants With Binding and Neutralizing Antibodies ^[7]

End point description

End point type

Primary

End point timeframe

Baseline to Day 720 or Study Exit

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistics were used to summarize the mean changes from vital signs from baseline. No statistical comparisons were made between arms.

End point values	Placebo/MT10109L 20U	Placebo/MT10109L 24U	Placebo/MT10109L 44U	MT10109L 20 U / MT10109L 20 U	MT10109L 24U/MT10109L 24U	MT10109L 20U/MT10109L 44U	MT10109L 24U/MT10109L 44U	MT10109L 44U /MT10109L 44U
Number of subjects analysed	55	56	118	116	108	128	123	253
Units: Number of Participant	0	0	0	0	2	0	0	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

The safety analyses were conducted in the Intent-to-Treat (ITT) population. All adverse events were collected from the signing of the ICF to 30 days after the participant's last study visit. Unless otherwise noted, safety results refer to TEAEs.

Adverse event reporting additional description

Treatment-Emergent Adverse Events (TEAEs)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Placebo/MT10109L 20 U

Reporting group description

The participant pool in this arm were from the MT10109L-001 lead-in study, who received Placebo in period 1 and MT10109L 20 U in period 2 in the GL area. Eligible participants from this study received 20 U in GL area in the open-label MT10109L-004 study.

Reporting group title

Placebo/MT10109L 24 U

Reporting group description

The participant pool in this arm were from the MT10109L-002 lead-in study, who received Placebo in period 1 and MT10109L 24 U in period 2. Eligible participants from this study continued receiving 24 U in the LCL area in the open-label MT10109L-004 study.

Reporting group title

Placebo/MT10109L 44 U

Reporting group description

The participant pool in this arm were from the MT10109L-005 and MT10109L-006 lead-in studies, who received Placebo in periods 1 & 2 in the GL and LCL areas. Eligible participants from this study received 20 U into the GL area and 24 U into the LCL area in the open-label MT10109L-004 study.

Reporting group title

MT10109L 20 U/20 U

Reporting group description

The participant pool in this arm were from the MT10109L-001 lead-in study, who received MT10109L 20 U each in period 1 and period 2 in the GL area. Eligible participants from this study continued receiving 20 in the GL area in the open-label MT10109L-004 study.

Reporting group title

MT10109L 24 U/24 U

Reporting group description

The participant pool in this arm were from the MT10109L-002 lead-in study, who received MT10109L 24 U each in period 1 and period 2 in the LCL area. Eligible participants from this study continued receiving 24 U in the LCL area in the open-label MT10109L-004 study.

Reporting group title

MT10109L 20 U/44 U

Reporting group description

The participant pool in this arm were from the from MT10109L-005 lead-in study, who received MT10109L 20 U in periods 1 and 2. Eligible participants from this study received 20 U into the GL area and 24 U into the LCL area in the open-label MT10109L-004 study.

Reporting group title

MT10109L 24 U/44 U

Reporting group description

The participant pool in this arm were from the MT10109L-006 lead-in study, who received MT10109L 24 U in the LCL area in periods 1 and 2. Eligible participants from this study continued to receive 20 U into the GL area and 24 U into the LCL area in the open-label MT10109L-004 study.

Reporting group title

MT10109L 44 U/44 U

Reporting group description

The participant pool in this arm were from the MT10109L-005 and MT10109L-006 lead-in studies, who received MT10109L 20 U into GL and 24 U into LCL in periods 1 & 2. Eligible participants from this study continued to receive 20 U into the GL area and 24 U into the LCL area in the open-label MT10109L-004 study.

Serious adverse events	Placebo/MT10109L 20 U	Placebo/MT10109L 24 U	Placebo/MT10109L 44 U	MT10109L 20 U/20 U	MT10109L 24 U/24 U	MT10109L 20 U/44 U	MT10109L 24 U/44 U	MT10109L 44 U/44 U
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 55 (5.45%)	1 / 56 (1.79%)	10 / 118 (8.47%)	8 / 116 (6.90%)	9 / 108 (8.33%)	7 / 128 (5.47%)	13 / 123 (10.57%)	13 / 253 (5.14%)
number of deaths (all causes)	0	0	0	2	0	0	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	2 / 118 (1.69%)	0 / 116 (0.00%)	0 / 108 (0.00%)	1 / 128 (0.78%)	3 / 123 (2.44%)	3 / 253 (1.19%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Basosquamous carcinoma A
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 118 (0.85%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Bone cancer
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 118 (0.85%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Breast cancer stage I
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Hormone receptor positive breast cancer
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 118 (0.85%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Intraductal proliferative breast lesion
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	1 / 108 (0.93%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Malignant melanoma in situ
subjects affected / exposed	1 / 55 (1.82%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	1 / 108 (0.93%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Papillary thyroid cancer
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	1 / 108 (0.93%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Plasma cell myeloma
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 118 (0.85%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Rectal cancer
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Renal cell carcinoma
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	1 / 108 (0.93%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Squamous cell carcinoma
subjects affected / exposed	0 / 55 (0.00%)	1 / 56 (1.79%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	1 / 128 (0.78%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 118 (0.85%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	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	0 / 0	0 / 0
Superficial spreading melanoma stage unspecified
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	1 / 116 (0.86%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	1 / 128 (0.78%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Surgical and medical procedures
Abortion induced
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 118 (0.85%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Immune system disorders
Allergy to arthropod sting
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Reproductive system and breast disorders
Endometriosis
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	1 / 128 (0.78%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	1 / 116 (0.86%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Psychiatric disorders
Bipolar disorder
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 118 (0.85%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	1 / 116 (0.86%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 118 (0.85%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Face injury
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	1 / 116 (0.86%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	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	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	1 / 116 (0.86%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Intentional overdose
subjects affected / exposed	1 / 55 (1.82%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	1 / 55 (1.82%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	1 / 55 (1.82%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Myocardial infarction
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	1 / 116 (0.86%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Facial paralysis
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	1 / 128 (0.78%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	2 / 123 (1.63%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Eye disorders
Conjunctival haemorrhage
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Gastrointestinal disorders
Colitis
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 118 (0.85%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 118 (0.85%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	1 / 108 (0.93%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Exostosis
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	1 / 108 (0.93%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	1 / 108 (0.93%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	1 / 118 (0.85%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	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	0 / 0	0 / 0
COVID 19
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	1 / 116 (0.86%)	1 / 108 (0.93%)	1 / 128 (0.78%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
COVID 19 Pneumonia
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	2 / 116 (1.72%)	1 / 108 (0.93%)	2 / 128 (1.56%)	0 / 123 (0.00%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	1 / 128 (0.78%)	0 / 123 (0.00%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endometritis
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Perirectal abscess
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	1 / 116 (0.86%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	0 / 123 (0.00%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	1 / 108 (0.93%)	0 / 128 (0.00%)	0 / 123 (0.00%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	0 / 108 (0.00%)	0 / 128 (0.00%)	1 / 123 (0.81%)	0 / 253 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Obesity
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	0 / 118 (0.00%)	0 / 116 (0.00%)	1 / 108 (0.93%)	0 / 128 (0.00%)	0 / 123 (0.00%)	1 / 253 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo/MT10109L 20 U	Placebo/MT10109L 24 U	Placebo/MT10109L 44 U	MT10109L 20 U/20 U	MT10109L 24 U/24 U	MT10109L 20 U/44 U	MT10109L 24 U/44 U	MT10109L 44 U/44 U
Total subjects affected by non serious adverse events
subjects affected / exposed	26 / 55 (47.27%)	23 / 56 (41.07%)	58 / 118 (49.15%)	54 / 116 (46.55%)	45 / 108 (41.67%)	50 / 128 (39.06%)	60 / 123 (48.78%)	128 / 253 (50.59%)
Injury, poisoning and procedural complications
Ligament Sprain
subjects affected / exposed	3 / 55 (5.45%)	0 / 56 (0.00%)	1 / 118 (0.85%)	3 / 116 (2.59%)	1 / 108 (0.93%)	0 / 128 (0.00%)	3 / 123 (2.44%)	3 / 253 (1.19%)
occurrences all number	3	0	1	3	1	0	3	3
Procedural pain
subjects affected / exposed	3 / 55 (5.45%)	0 / 56 (0.00%)	0 / 118 (0.00%)	3 / 116 (2.59%)	0 / 108 (0.00%)	0 / 128 (0.00%)	4 / 123 (3.25%)	2 / 253 (0.79%)
occurrences all number	3	0	0	3	0	0	4	2
Vascular disorders
Hypertension
subjects affected / exposed	4 / 55 (7.27%)	2 / 56 (3.57%)	3 / 118 (2.54%)	5 / 116 (4.31%)	3 / 108 (2.78%)	3 / 128 (2.34%)	6 / 123 (4.88%)	9 / 253 (3.56%)
occurrences all number	4	2	3	5	3	3	6	9
Nervous system disorders
Headache
subjects affected / exposed	12 / 55 (21.82%)	1 / 56 (1.79%)	11 / 118 (9.32%)	12 / 116 (10.34%)	5 / 108 (4.63%)	13 / 128 (10.16%)	13 / 123 (10.57%)	27 / 253 (10.67%)
occurrences all number	12	1	11	12	5	13	13	27
General disorders and administration site conditions
Injection site bruising
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	8 / 118 (6.78%)	3 / 116 (2.59%)	0 / 108 (0.00%)	4 / 128 (3.13%)	12 / 123 (9.76%)	20 / 253 (7.91%)
occurrences all number	0	0	8	3	0	4	12	20
Injection site haemorrhage
subjects affected / exposed	1 / 55 (1.82%)	3 / 56 (5.36%)	8 / 118 (6.78%)	0 / 116 (0.00%)	6 / 108 (5.56%)	2 / 128 (1.56%)	7 / 123 (5.69%)	11 / 253 (4.35%)
occurrences all number	1	3	8	0	6	2	7	11
Injection site pain
subjects affected / exposed	8 / 55 (14.55%)	0 / 56 (0.00%)	10 / 118 (8.47%)	17 / 116 (14.66%)	0 / 108 (0.00%)	8 / 128 (6.25%)	17 / 123 (13.82%)	23 / 253 (9.09%)
occurrences all number	8	0	10	17	0	8	17	23
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 55 (1.82%)	0 / 56 (0.00%)	6 / 118 (5.08%)	2 / 116 (1.72%)	2 / 108 (1.85%)	3 / 128 (2.34%)	4 / 123 (3.25%)	5 / 253 (1.98%)
occurrences all number	1	0	6	2	2	3	4	5
Infections and infestations
COVID-19
subjects affected / exposed	7 / 55 (12.73%)	12 / 56 (21.43%)	22 / 118 (18.64%)	18 / 116 (15.52%)	31 / 108 (28.70%)	20 / 128 (15.63%)	22 / 123 (17.89%)	47 / 253 (18.58%)
occurrences all number	7	12	22	18	31	20	22	47
Influenza
subjects affected / exposed	2 / 55 (3.64%)	0 / 56 (0.00%)	6 / 118 (5.08%)	0 / 116 (0.00%)	1 / 108 (0.93%)	2 / 128 (1.56%)	1 / 123 (0.81%)	1 / 253 (0.40%)
occurrences all number	2	0	6	0	1	2	1	1
Nasopharyngitis
subjects affected / exposed	6 / 55 (10.91%)	4 / 56 (7.14%)	15 / 118 (12.71%)	9 / 116 (7.76%)	8 / 108 (7.41%)	9 / 128 (7.03%)	17 / 123 (13.82%)	31 / 253 (12.25%)
occurrences all number	6	4	15	9	8	9	17	31
Sinusitis
subjects affected / exposed	2 / 55 (3.64%)	5 / 56 (8.93%)	4 / 118 (3.39%)	3 / 116 (2.59%)	4 / 108 (3.70%)	3 / 128 (2.34%)	3 / 123 (2.44%)	7 / 253 (2.77%)
occurrences all number	2	5	4	3	4	3	3	7
Upper respiratory tract infection
subjects affected / exposed	0 / 55 (0.00%)	0 / 56 (0.00%)	11 / 118 (9.32%)	6 / 116 (5.17%)	5 / 108 (4.63%)	7 / 128 (5.47%)	5 / 123 (4.07%)	15 / 253 (5.93%)
occurrences all number	0	0	11	6	5	7	5	15

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Were there any global substantial amendments to the protocol? Yes

30 Jun 2019

Substantial Changes: Changes were made to integrate feedback and recommendations from health authorities for the lead-in Phase 3 studies and improve clarity of study processes

31 Oct 2019

Substantial Changes: The overall rationale for the changes implemented in this open-label, extension study was to integrate feedback and recommendations received from health authorities to date on the lead-in studies.

31 Mar 2020

EU Specific Amendment 1: The overall rationale for the changes implemented in this open-label, extension study was to integrate feedback and recommendations received from health authorities.

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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Clinical Trial Results:
A Multicenter, Long-term, Open-label Study to Evaluate the Safety of MT10109L (NivobotulinumtoxinA) for the Treatment of Glabellar Lines and Lateral Canthal Lines

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Primary: Number of Participants Who Experienced Any Adverse Event (AE)

Primary: Number of Participants Who Experienced Any Adverse Event (AE)

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Primary: Mean Change From Baseline in Pulse Rate (Beats Per Minute)

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Clinical trials

Clinical Trial Results: A Multicenter, Long-term, Open-label Study to Evaluate the Safety of MT10109L (NivobotulinumtoxinA) for the Treatment of Glabellar Lines and Lateral Canthal Lines

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants Who Experienced Any Adverse Event (AE)

Primary: Number of Participants Who Experienced Any Adverse Event (AE)

Primary: Number of Participants Who Experienced Treatment-Related Adverse Events (TEAEs)

Primary: Number of Participants Who Experienced Treatment-Related Adverse Events (TEAEs)

Primary: Mean Change From Baseline in Pulse Rate (Beats Per Minute)

Primary: Mean Change From Baseline in Pulse Rate (Beats Per Minute)

Primary: Mean Change From Baseline in Systolic Blood Pressure (mm Hg)

Primary: Mean Change From Baseline in Systolic Blood Pressure (mm Hg)

Primary: Mean Change From Baseline in Diastolic Blood Pressure (mm Hg)

Primary: Mean Change From Baseline in Diastolic Blood Pressure (mm Hg)

Primary: Mean Change From Baseline in Respiratory Rate (Breaths Per Minute)

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Primary: Number of Participants With Binding and Neutralizing Antibodies

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Substantial protocol amendments (globally)

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Clinical Trial Results:
A Multicenter, Long-term, Open-label Study to Evaluate the Safety of MT10109L (NivobotulinumtoxinA) for the Treatment of Glabellar Lines and Lateral Canthal Lines