Clinical Trial Results:
A prospective, open-label, multi-center, repeat-dose study to investigate the safety and efficacy of NT 201 (incobotulinumtoxinA) in the combined treatment of upper facial lines (horizontal forehead lines, glabellar frown lines, and lateral periorbital lines)
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Summary
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EudraCT number |
2014-003770-16 |
Trial protocol |
DE |
Global end of trial date |
08 Dec 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Jan 2018
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First version publication date |
03 Jan 2018
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MRZ60201_3100_1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Merz Pharmaceuticals GmbH
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Sponsor organisation address |
Eckenheimer Landstrasse 100, Frankfurt/M, Germany, 60318
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Public contact |
Public Disclosure Manager, Merz Pharmaceuticals GmbH, +49 69 1503 1, clinicaltrials@merz.de
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Scientific contact |
Public Disclosure Manager, Merz Pharmaceuticals GmbH, +49 69 1503 1, clinicaltrials@merz.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Mar 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Dec 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The purpose of this study is to investigate the safety and tolerability of 54 to 64 Units of NT 201 intramuscularly administered in subjects with moderate to severe upper facial lines (UFL) during repeat-dose treatment of these lines.
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Protection of trial subjects |
High medical and ethical standards were followed in accordance with Good Clinical Practice and other applicable regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Apr 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 140
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Worldwide total number of subjects |
140
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EEA total number of subjects |
140
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
131
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From 65 to 84 years |
9
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85 years and over |
0
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Recruitment
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Recruitment details |
The clinical study was conducted at 10 sites in Germany from 30 April 2015 to 08 December 2016. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects with moderate to severe lines (horizontal forehead lines [HFL], glabellar frown lines [GFL], and lateral periorbital lines [LPL]) at maximum contraction were enrolled. Total 145 subjects were screened, of which 140 subjects were enrolled and treated with 54 to 64 Units of IncobotulinumtoxinA, and of these 125 subjects completed the study. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall period
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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IncobotulinumtoxinA 54 to 64 Units | ||||||||||||||||||
Arm description |
Subjects received a total volume of 1.35 to 1.6 milliliter (mL) of incobotulinumtoxinA (Xeomin) with a maximum of 54 to 64 units per injection treatment via intramuscular injection into the 3 facial areas (HFL, GFL and LPL) on Day 1 of each treatment cycle for up to a maximum of 4 treatment cycles. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
IncobotulinumtoxinA
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Investigational medicinal product code |
NT 201
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Other name |
Xeomin; Botulinum toxin type A (150 kiloDalton) free from complexing proteins
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Subjects received a total volume of 1.35 to 1.6 mL of incobotulinumtoxinA with a maximum of 54 to 64 units per injection treatment via intramuscular injection into the 3 facial areas (HFL, GFL and LPL) on Day 1 of each treatment cycle for up to a maximum of 4 treatment cycles.
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Baseline characteristics reporting groups
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Reporting group title |
IncobotulinumtoxinA 54 to 64 Units
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Reporting group description |
Subjects received a total volume of 1.35 to 1.6 milliliter (mL) of incobotulinumtoxinA (Xeomin) with a maximum of 54 to 64 units per injection treatment via intramuscular injection into the 3 facial areas (HFL, GFL and LPL) on Day 1 of each treatment cycle for up to a maximum of 4 treatment cycles. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
IncobotulinumtoxinA 54 to 64 Units
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Reporting group description |
Subjects received a total volume of 1.35 to 1.6 milliliter (mL) of incobotulinumtoxinA (Xeomin) with a maximum of 54 to 64 units per injection treatment via intramuscular injection into the 3 facial areas (HFL, GFL and LPL) on Day 1 of each treatment cycle for up to a maximum of 4 treatment cycles. | ||
Subject analysis set title |
Safety Evaluation Set (SES)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The SES included all subjects who were exposed to study medication at least once.
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Subject analysis set title |
Full Analysis Set (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The FAS included all subjects in the SES with at least one post-injection efficacy assessment.
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End point title |
Number of Subjects with Treatment-emergent Adverse Events (TEAEs) [1] | ||||||
End point description |
TEAEs were defined as adverse events (AEs) with onset or worsening or change to serious during or after 1st injection of study medication up to and including the end of study visit. Values reported here refer to the number of overall subjects affected.
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End point type |
Primary
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End point timeframe |
From the time point of first injection up to end of study visit (Day 480)
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| 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: Only descriptive data was planned to be reported for this endpoint. |
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| Notes [2] - SES |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects with TEAEs per Treatment Cycle | ||||||||||||||
End point description |
TEAEs were defined as AEs with onset or worsening or change to serious during or after 1st injection of study medication up to and including the end of study visit. Values reported here refer to the number of subjects affected per treatment cycle. Here, 'n' indicated number of subjects for which the variable was assessed at each of the injection cycles.
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End point type |
Secondary
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End point timeframe |
From the time point of first injection up to end of study visit (Day 480)
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| Notes [3] - SES |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of Subjects with Treatment Emergent Adverse Events of Special Interest (TEAESIs) Overall and per Injection Cycle | ||||||||||||||||
End point description |
TEAEs were defined as AEs with onset or worsening or change to serious during or after 1st injection of study medication up to and including the end of study visit. AEs occurring after treatment that were thought to possibly indicate toxin spread were defined as adverse events of special interests (AESIs). Values reported here refer to the number of subjects affected per treatment cycle.
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End point type |
Secondary
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End point timeframe |
From the time point of first injection until end of study visit (Day 480)
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| Notes [4] - SES |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Responders Rate at Maximum Contraction for GFL, HFL, and LPL as Assessed by the Investigator | ||||||||||||||||||||||||||||||||
End point description |
Response at maximum contraction was defined as a score of 0 or 1 on the Merz Aesthetics Scale (MAS) as assessed by the investigator. MAS is a validated 5-point scale for the treated areas. The five points of the scales show the evident severity of aging processes of the aesthetic lines. The severity grades of the scale are 0 for none, 1 for mild, 2 for moderate, 3 for severe, and 4 for very severe lines. Here, 'n' indicated number of subjects for which the variable was assessed at each of the injection cycles.
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End point type |
Secondary
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End point timeframe |
Day 30 of each injection cycle
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| Notes [5] - FAS |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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End point title |
Responders Rate for Overall Upper Face Appearance as Assessed by the Subject | ||||||||||||||||
End point description |
Response was defined as a score of much improved (+2) or very much improved (+3) on the Global impression of change scale (GICS) as assessed by the subject. GICS is a 7-point likert scale that range from -3, very much worse to +3, very much improved. Here, 'n' indicated number of subjects for which the variable was assessed at each of the injection cycles.
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End point type |
Secondary
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End point timeframe |
Day 30 of each injection cycle
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| Notes [6] - FAS |
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the time point of first injection up to end of study visit (Day 480)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
IncobotulinumtoxinA 54 to 64 Units
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Reporting group description |
Subjects received a total volume of 1.35 to 1.6 mL of incobotulinumtoxinA with a maximum of 54 to 64 units per injection treatment via intramuscular injection into the 3 facial areas (HFL, GFL and LPL) on Day 1 of each treatment cycle for up to a maximum of 4 treatment cycles. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
