Clinical Trial Results:
Long-Term, Follow-up Study of Subjects Who Completed Phase III Trials of ATX-101-10-16 or ATX-101-10-17 (Sodium Deoxycholate Injection) for the Reduction of Localized Subcutaneous Fat in the Submental Area
|
Summary
|
|
EudraCT number |
2011-005026-21 |
Trial protocol |
DE |
Global end of trial date |
13 Dec 2013
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
30 Sep 2018
|
First version publication date |
30 Sep 2018
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
1403740
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02052622 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Allergan Pharmaceuticals International Limited
|
||
Sponsor organisation address |
Clonshaugh Industrial Estate, Coolock, Dublin 17, Ireland, D17 E400
|
||
Public contact |
Clinical Trials Registry Team, Allergan Pharmaceuticals International Limited, 001 877‐277‐8566, IR-CTRegistration@allergan.com
|
||
Scientific contact |
Therapeutic Area Head, Allergan Pharmaceuticals International Limited, 001 877-277-8566, IR-CTRegistration@Allergan.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
13 Dec 2013
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
13 Dec 2013
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The objective of this non-treatment, placebo-controlled, observational, 24-month follow-up study was to evaluate the long-term efficacy and safety of subcutaneous (SC) injections of deoxycholic acid (ATX-101) in the submental area. No treatment was administered in this study. Participants who previously received deoxycholic acid injections in studies ATX-101-10-16 or ATX-101-10-17 were enrolled in this non-treatment observational follow-up study to further evaluate safety and efficacy.
|
||
Protection of trial subjects |
All study participants were required to read and sign an Informed Consent Form.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Feb 2012
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Efficacy, Safety | ||
Long term follow-up duration |
24 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Germany: 201
|
||
Worldwide total number of subjects |
201
|
||
EEA total number of subjects |
201
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
199
|
||
From 65 to 84 years |
2
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||
Screening details |
A subset of participants at selected centers who had successfully completed Phase 3 clinical studies ATX-101-10-16 or ATX-101-10-17 for the reduction of submental fat were enrolled in this non-treatment observational long-term follow-up (LTFU) study. | ||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||
|
Arm title
|
Deoxycholic Acid Injection, 5 mg/mL | ||||||||||||||||||||
Arm description |
Non-treatment observational follow-up study: Participants were previously treated with deoxycholic acid injection, 5 mg/mL, in studies ATX-101-10-16 or ATX-101-10-17. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Deoxycholic acid Injection
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
Kybella
|
||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||
Dosage and administration details |
Previously treated with deoxycholic acid injection, 5 mg/mL, in studies ATX-101-10-16 or ATX-101-10-17
|
||||||||||||||||||||
|
Arm title
|
Deoxycholic Acid Injection, 10 mg/mL | ||||||||||||||||||||
Arm description |
Non-treatment observational follow-up study: Participants were previously treated with deoxycholic acid injection, 10 mg/mL, in studies ATX-101-10-16 or ATX-101-10-17. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Deoxycholic acid Injection
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
Kybella
|
||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||
Dosage and administration details |
Previously treated with deoxycholic acid injection, 10 mg/mL, in studies ATX-101-10-16 or ATX-101-10-17
|
||||||||||||||||||||
|
Arm title
|
Placebo | ||||||||||||||||||||
Arm description |
Non-treatment observational follow-up study: Participants were previously treated with placebo in studies ATX-101-10-16 or ATX-101-10-17. | ||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||
Investigational medicinal product name |
Placebo, 10 mM sodium phosphate, 0.9% [w/v] sodium chloride in water for injection
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
|||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||
Dosage and administration details |
Previously treated with placebo in studies ATX-101-10-16 or ATX-101-10-17
|
||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Deoxycholic Acid Injection, 5 mg/mL
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Non-treatment observational follow-up study: Participants were previously treated with deoxycholic acid injection, 5 mg/mL, in studies ATX-101-10-16 or ATX-101-10-17. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Deoxycholic Acid Injection, 10 mg/mL
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Non-treatment observational follow-up study: Participants were previously treated with deoxycholic acid injection, 10 mg/mL, in studies ATX-101-10-16 or ATX-101-10-17. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Non-treatment observational follow-up study: Participants were previously treated with placebo in studies ATX-101-10-16 or ATX-101-10-17. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Deoxycholic Acid Injection, 5 mg/mL
|
||
Reporting group description |
Non-treatment observational follow-up study: Participants were previously treated with deoxycholic acid injection, 5 mg/mL, in studies ATX-101-10-16 or ATX-101-10-17. | ||
Reporting group title |
Deoxycholic Acid Injection, 10 mg/mL
|
||
Reporting group description |
Non-treatment observational follow-up study: Participants were previously treated with deoxycholic acid injection, 10 mg/mL, in studies ATX-101-10-16 or ATX-101-10-17. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
Non-treatment observational follow-up study: Participants were previously treated with placebo in studies ATX-101-10-16 or ATX-101-10-17. | ||
|
|||||||||||||||||
End point title |
Percentage of Participants Maintaining Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) 1-Grade Response During the 24 Months of Follow up, i.e. % of Participants who were CR-SMFRS 1-Grade Responders at both LTFU Baseline and at 24-Month Visit [1] | ||||||||||||||||
End point description |
The CR-SMFRS was based on the investigator’s clinical evaluation of the participant's chin and neck area using a 5-point ordinal scale (0 to 4) with 0=Absent Submental Convexity: no localized submental fat evident; 1=Mild Submental Convexity: minimal, localized submental fat; 2=Moderate Submental Convexity: prominent, localized submental fat; 3=Severe Submental Convexity; a marked amount of chin fat; and 4=Extreme Submental Convexity: marked, localized submental fat. 1-grade response=At least a 1-grade reduction from original study baseline in the CR-SMFRS assessment. The full analysis set included all participants who received a clearly identifiable treatment in the previous study and had at least one visit in the LTFU study. Participants were included in the analysis according to their randomized treatment assignment. Missing values at Month 24 were imputed using LOCF. Non-responders at LTFU baseline in each treatment group (including placebo) were not included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
LTFU Baseline (Month 0) to Month 24
|
||||||||||||||||
| 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: No inferential statistical analyses were performed for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Participants with Maintenance of Response as Assessed by the Subject Satisfaction Rating Scale (SSRS) During the 24 Months of Follow up, i.e. % of Participants who were SSRS Responders at both LTFU Baseline and at 24-Month Visit [2] | ||||||||||||||||
End point description |
For the SSRS, the participant was asked to answer the question: “Considering your appearance in association with your face and chin, how satisfied do you feel with your appearance at the present time?” using a 7-point scale: 0=Extremely dissatisfied, 1=Dissatisfied, 2=Slightly dissatisfied, 3=neither satisfied nor dissatisfied, 4=Slightly satisfied, 5=Satisfied, and 6=Extremely satisfied. SSRS responder was a participant whose response was ≥ 4. A positive change from Baseline indicates improvement. The full analysis set included all participants who received a clearly identifiable treatment in the previous study and had at least one visit in the LTFU study. Participants were included in the analysis according to their randomized treatment assignment. Missing values at Month 24 were imputed using last observation carried forward (LOCF). Non-responders at LTFU baseline in each treatment group (including placebo) were not included in the analysis.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
LTFU Baseline (Month 0) to Month 24
|
||||||||||||||||
| 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: No inferential statistical analyses were performed for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Participants Maintaining Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) 2-Grade Response During the 24 Months of Follow up, i.e. % of Participants who were CR-SMFRS 2-Grade Responders at both LTFU Baseline and at 24-Month Visit | ||||||||||||||||
End point description |
The CR-SMFRS was based on the investigator’s clinical evaluation of the participant's chin and neck area using a 5-point ordinal scale (0 to 4) with 0=Absent Submental Convexity: no localized submental fat evident; 1=Mild Submental Convexity: minimal, localized submental fat; 2=Moderate Submental Convexity: prominent, localized submental fat; 3=Severe Submental Convexity; a marked amount of chin fat; and 4=Extreme Submental Convexity: marked, localized submental fat. 2-grade response=At least a 2-grade reduction from original study baseline in the CR-SMFRS assessment. The full analysis set included all participants who received a clearly identifiable treatment in the previous study and had at least one visit in the LTFU study. Participants were included in the analysis according to their randomized treatment assignment. Missing values at Month 24 were imputed using LOCF. Non-responders at LTFU baseline in each treatment group (including placebo) were not included in the analysis.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
LTFU Baseline (Month 0) to Month 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Patient-Reported Submental Fat Impact Scale (PR-SMFIS) | ||||||||||||||||||||||||
End point description |
The PR-SMFIS assessed the impact of submental fat on self-perception of 6 emotional and visual characteristics related to the appearance of submental fullness (unhappy, bothered, self-conscious, embarrassed, look older, and look overweight) as evaluated by the participant. Each item was rated on an 11-point numeric scale from 0 to 10. Scores for the 6 items were averaged to generate a PR-SMFIS total scale score ranging from 0 to 10 where low scores reflect a positive impact and high scores reflect a negative impact. The full analysis set included all participants who received a clearly identifiable treatment in the previous study and had at least one visit in the LTFU study. Participants were included in the analysis according to their randomized treatment assignment. Here, "n" represents the number of participants evaluated at specific time points.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
LTFU Baseline (Month 0) to Month 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Participants Maintaining Composite SMFRS 1-Grade Response During the 24 Months of Follow up, i.e. % of Participants who were Composite SMFRS 1-Grade Responders at both LTFU Baseline and at 24-Month Visit | ||||||||||||||||
End point description |
Participants who had at least a 1-grade reduction in both the CR-SMFRS and PR-SMFRS from the original baseline value in the predecessor study were defined as composite SMFRS-1 responders. The full analysis set included all participants who received a clearly identifiable treatment in the previous study and had at least one visit in the LTFU study. Participants were included in the analysis according to their randomized treatment assignment. Missing values at Month 24 were imputed using last observation carried forward (LOCF). Non-responders at LTFU baseline in each treatment group (including placebo) were not included in the analysis for this endpoint.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
LTFU Baseline (Month 0) to Month 24
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Participants with at Least One Treatment-Emergent Adverse Event (TEAE) | ||||||||||||||||
End point description |
An adverse event was any undesirable medical occurrence or worsening of an existing condition, irrespective of whether the event was considered treatment-related. A treatment-emergent adverse event was defined as an adverse event with an onset that occurs after receiving treatment. The safety set included all participants who received a clearly identifiable treatment in the previous study. Participants were included in the analysis according to the actual treatments received.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to approximately 24 months
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Participants with Treatment-emergent Adverse Events Associated with the Treatment Area (Drug-related) | ||||||||||||||||
End point description |
An adverse event was any undesirable medical occurrence or worsening of an existing condition, irrespective of whether the event was considered treatment-related. A treatment-emergent adverse event was defined as an adverse event with an onset that occurs after receiving treatment. The safety set included all participants who received a clearly identifiable treatment in the previous study. Participants were included in the analysis according to the actual treatments received.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to approximately 24 months
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Participants with Treatment-emergent Adverse Events of Special Interest (AESIs) | ||||||||||||||||
End point description |
An adverse event was any undesirable medical occurrence or worsening of an existing condition, irrespective of whether the event was considered treatment-related. A treatment-emergent adverse event was defined as an adverse event with an onset that occurs after receiving treatment. AESIs for this study are common treatment reactions (consistently reported for overall AEs, treatment area-related AEs, or study-drug-related AEs) that were observed in earlier deoxycholic acid injection studies and identified as likely to be related to the injection procedure. The safety set included all participants who received a clearly identifiable treatment in the previous study. Participants were included in the analysis according to the actual treatments received.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to approximately 24 months
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information [1]
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Approximately 24 months
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Deoxycholic Acid Injection, 5 mg/mL
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Non-treatment observational follow-up study: Participants were previously treated with deoxycholic acid injection, 5 mg/mL, in studies ATX-101-10-16 or ATX-101-10-17. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Deoxycholic Acid Injection, 10 mg/mL
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Non-treatment observational follow-up study: Participants were previously treated with deoxycholic acid injection, 10 mg/mL, in studies ATX-101-10-16 or ATX-101-10-17. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Non-treatment observational follow-up study: Participants were previously treated with placebo in studies ATX-101-10-16 or ATX-101-10-17. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No non-serious adverse events occurred at the 5% threshold. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
