Trial Outcomes & Findings for The Treatment of Glabellar Frown Lines (NCT NCT02096081)

NCT ID: NCT02096081

Last Updated: 2017-10-19

Results Overview

Response defined as ≥ 1 point improvement from baseline (prior to treatment) on the Facial Wrinkle Scale at maximum frown as rated by an independent masked panel of physicians specifically qualified to assess study photographs using subject photographs at 1 month from treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 250 participants
• Primary outcome timeframe: 1 Month from baseline
• Results posted on: 2017-10-19

Participant Flow

Participant milestones

Measure	IncobotulinumtoxinA 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Overall Study STARTED	122	128
Overall Study COMPLETED	119	124
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Treatment of Glabellar Frown Lines

Baseline characteristics by cohort

Measure	IncobotulinumtoxinA n=122 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=128 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	Total n=250 Participants Total of all reporting groups
Age, Continuous	39.3 years STANDARD_DEVIATION 7.4 • n=5 Participants	39.4 years STANDARD_DEVIATION 7.8 • n=7 Participants	39.3 years STANDARD_DEVIATION 7.6 • n=5 Participants
Sex: Female, Male Female	122 Participants n=5 Participants	128 Participants n=7 Participants	250 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=5 Participants	35 Participants n=7 Participants	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	99 Participants n=5 Participants	93 Participants n=7 Participants	192 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) White	104 Participants n=5 Participants	107 Participants n=7 Participants	211 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 Month from baseline

Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.

Response defined as ≥ 1 point improvement from baseline (prior to treatment) on the Facial Wrinkle Scale at maximum frown as rated by an independent masked panel of physicians specifically qualified to assess study photographs using subject photographs at 1 month from treatment.

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Efficacy, Measured as the Percentage of Participants Who Responded to Treatment	95.7 percentage of participants	99.2 percentage of participants

SECONDARY outcome

Timeframe: 2 months from baseline

Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.

Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by an independent masked panel of physicians specifically qualified to assess study photographs using subject photographs at 2 months from baseline.

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Response at Maximum Frown Rated by Independent Rater	89.7 percentage of participants	95.0 percentage of participants

SECONDARY outcome

Timeframe: 3 months from baseline

Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.

Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by an independent masked panel of physicians specifically qualified to assess study photographs using subject photographs at 3 months from baseline.

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Response at Maximum Frown Rated by Independent Rater	80.2 percentage of participants	80.7 percentage of participants

SECONDARY outcome

Timeframe: 4 months from baseline

Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.

Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by an independent masked panel of physicians specifically qualified to assess study photographs using subject photographs at 4 months from baseline.

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Response at Maximum Frown Rated by Independent Rater	62.1 percentage of participants	67.2 percentage of participants

SECONDARY outcome

Timeframe: 1 month from baseline

Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.

Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by the treating physicians using subject photographs at 1 month from treatment.

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Response at Maximum Frown Rated by Treating Physician	93.1 percentage of participants	95.8 percentage of participants

SECONDARY outcome

Timeframe: 2 months from baseline

Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.

Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by the treating physicians using subject photographs at 2 months from treatment.

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Response at Maximum Frown Rated by Treating Physician	87.1 percentage of participants	89.9 percentage of participants

SECONDARY outcome

Timeframe: 3 months from baseline

Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.

Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by the treating physicians using subject photographs at 3 months from treatment.

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Response at Maximum Frown Rated by Treating Physician	75.0 percentage of participants	76.5 percentage of participants

SECONDARY outcome

Timeframe: 4 months from baseline

Population: All efficacy analyses were performed on the per protocol set (PPS) defined as the subset of subjects in the FAS for whom no major protocol deviations were identified.

Response defined as ≥ 1 point improvement from baseline on the Facial Wrinkle Scale (0=None to 3=severe) at maximum frown as rated by the treating physicians using subject photographs at 4 months from treatment.

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Response at Maximum Frown Rated by Treating Physician	58.6 percentage of participants	60.5 percentage of participants

SECONDARY outcome

Timeframe: 1 month from baseline

Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.

Assessment of subject treatment satisfaction by subject questionnaire and diary at 1 month from treatment. Extremely satisfied, satisfied, and slightly satisfied were categorized as "Satisfaction" and extremely dissatisfied, dissatisfied, and slightly dissatisfied were categorized as "Dissatisfaction." Subjects with missing data were categorized as "Missing."

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Subject Satisfaction Satisfaction	112 participants	116 participants
Subject Satisfaction Dissatifaction	3 participants	3 participants
Subject Satisfaction Missing	1 participants	0 participants

SECONDARY outcome

Timeframe: 2 months from baseline

Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.

Assessment of subject treatment satisfaction by subject questionnaire and diary at 2 months from treatment. Extremely satisfied, satisfied, and slightly satisfied were categorized as "Satisfaction" and extremely dissatisfied, dissatisfied, and slightly dissatisfied were categorized as "Dissatisfaction." Subjects with missing data were categorized as "Missing."

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Subject Satisfaction Satisfied	110 participants	113 participants
Subject Satisfaction Dissatisfied	5 participants	6 participants
Subject Satisfaction Missing	1 participants	0 participants

SECONDARY outcome

Timeframe: 3 months from baseline

Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.

Assessment of subject treatment satisfaction by subject questionnaire and diary at 3 months from treatment. Extremely satisfied, satisfied, and slightly satisfied were categorized as "Satisfaction" and extremely dissatisfied, dissatisfied, and slightly dissatisfied were categorized as "Dissatisfaction." Subjects with missing data were categorized as "Missing."

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Subject Satisfaction Satisfaction	108 participants	108 participants
Subject Satisfaction Dissatisfaction	7 participants	10 participants
Subject Satisfaction Missing	1 participants	1 participants

SECONDARY outcome

Timeframe: 4 months from baseline

Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.

Assessment of subject treatment satisfaction by subject questionnaire and diary at 4 months from treatment. Extremely satisfied, satisfied, and slightly satisfied were categorized as "Satisfaction" and extremely dissatisfied, dissatisfied, and slightly dissatisfied were categorized as "Dissatisfaction." Subjects with missing data were categorized as "Missing."

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Subject Satisfaction Satisfaction	107 participants	104 participants
Subject Satisfaction Dissatisfaction	8 participants	11 participants
Subject Satisfaction Missing	1 participants	4 participants

SECONDARY outcome

Timeframe: Open-ended time frame for the 4 month study duration. Data for onset and peak effect is recorded in the subject diary.

Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.

Assessment of subject perception of date of treatment onset using a take-home diary

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Subject Perception of Treatment Onset	3.0 days Interval 1.0 to 14.0	3.0 days Interval 1.0 to 14.0

SECONDARY outcome

Timeframe: Open-ended time frame for the 4 month study duration. Data for onset and peak effect is recorded in the subject diary.

Population: This endpoint was analyzed using observed cases in the per protocol set (PPS), defined as the subset of subjects in the FAS from whom no major protocol deviations were identified.

Assessment of subject perception of date of treatment peak effect using a take-home diary

Outcome measures

Measure	IncobotulinumtoxinA n=116 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=119 Participants 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Subject Perception of Treatment Peak Effect Within 4 weeks	108 participants	113 participants
Subject Perception of Treatment Peak Effect Longer than 4 weeks	7 participants	4 participants
Subject Perception of Treatment Peak Effect Missing	1 participants	2 participants

Adverse Events

IncobotulinumtoxinA

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

OnabotulinumtoxinA

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	IncobotulinumtoxinA n=122 participants at risk 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U/injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=128 participants at risk 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U/injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Infections and infestations Human ehrlichiosis	0.82% 1/122 • Number of events 1 • Adverse events were collected during the entire study period (4 months). Adverse events were not followed-up after the final study visit/safety visit, which was scheduled for 4 months post-treatment.	0.00% 0/128 • Adverse events were collected during the entire study period (4 months). Adverse events were not followed-up after the final study visit/safety visit, which was scheduled for 4 months post-treatment.
Infections and infestations Atypical pneumonia	0.00% 0/122 • Adverse events were collected during the entire study period (4 months). Adverse events were not followed-up after the final study visit/safety visit, which was scheduled for 4 months post-treatment.	0.78% 1/128 • Number of events 1 • Adverse events were collected during the entire study period (4 months). Adverse events were not followed-up after the final study visit/safety visit, which was scheduled for 4 months post-treatment.

Other adverse events

Measure	IncobotulinumtoxinA n=122 participants at risk 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. IncobotulinumtoxinA: 20U/injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection	OnabotulinumtoxinA n=128 participants at risk 20U injection: equal aliquots of 0.1 mL (4U) to 5 injection points. OnabotulinumtoxinA: 20U/injection: equal aliquots of 0.1 mL (4U) to 5 injection points; mode of application: intramuscular injection
Nervous system disorders Headache	5.7% 7/122 • Number of events 7 • Adverse events were collected during the entire study period (4 months). Adverse events were not followed-up after the final study visit/safety visit, which was scheduled for 4 months post-treatment.	3.9% 5/128 • Number of events 5 • Adverse events were collected during the entire study period (4 months). Adverse events were not followed-up after the final study visit/safety visit, which was scheduled for 4 months post-treatment.
Musculoskeletal and connective tissue disorders Facial Asymmetry	1.6% 2/122 • Number of events 2 • Adverse events were collected during the entire study period (4 months). Adverse events were not followed-up after the final study visit/safety visit, which was scheduled for 4 months post-treatment.	2.3% 3/128 • Number of events 3 • Adverse events were collected during the entire study period (4 months). Adverse events were not followed-up after the final study visit/safety visit, which was scheduled for 4 months post-treatment.

Additional Information

Michelle Widmann

Merz North America, Inc.

Phone: 919-582-8238

Email: Michelle.Widmann@merz.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place