Trial Outcomes & Findings for A Safety and Efficacy Study of OnabotulinumtoxinA in Upper Facial Rhytides (NCT NCT02261493)

Last Updated: 2017-07-25

Results Overview

The Investigator and subject each assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 2-grade improvement from baseline assessed by both the Investigator and the subject are reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

787 participants

Primary outcome timeframe

Baseline, Day 30

Results posted on

2017-07-25

Participant Flow

Subjects were randomized to placebo, onabotulinumtoxinA Dose A, or onabotulinumtoxinA Dose B in Period 1. Subjects randomized to receive placebo or Dose B in Period 1, who subsequently continued to Period 2, received onabotulinumtoxinA Dose A in Period 2.

Participant milestones

Participant milestones
Measure	Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.	OnabotulinumtoxinA Dose B OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	OnabotulinumtoxinA Dose A OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Overall Study STARTED	156	318	313
Overall Study COMPLETED	126	271	287
Overall Study NOT COMPLETED	30	47	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.	OnabotulinumtoxinA Dose B OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	OnabotulinumtoxinA Dose A OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Overall Study Noncompliance	0	0	2
Overall Study Physician Decision	0	1	0
Overall Study Undisclosed alcohol abuse	0	1	0
Overall Study Protocol Violation	1	0	0
Overall Study Personal Reasons	14	14	16
Overall Study Lost to Follow-up	14	27	8
Overall Study Pregnancy	1	2	0
Overall Study Lack of Efficacy	0	1	0
Overall Study Adverse Event	0	1	0

Baseline Characteristics

A Safety and Efficacy Study of OnabotulinumtoxinA in Upper Facial Rhytides

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A n=156 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.	OnabotulinumtoxinA Dose B n=318 Participants OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	OnabotulinumtoxinA Dose A n=313 Participants OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	Total n=787 Participants Total of all reporting groups
Age, Customized <65 years	147 Participants n=5 Participants	300 Participants n=7 Participants	302 Participants n=5 Participants	749 Participants n=4 Participants
Age, Customized >=65 years	9 Participants n=5 Participants	18 Participants n=7 Participants	11 Participants n=5 Participants	38 Participants n=4 Participants
Sex: Female, Male Female	140 Participants n=5 Participants	278 Participants n=7 Participants	284 Participants n=5 Participants	702 Participants n=4 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	40 Participants n=7 Participants	29 Participants n=5 Participants	85 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-Treat: all randomized subjects

Outcome measures

Outcome measures
Measure	Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A n=156 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.	OnabotulinumtoxinA Dose B n=318 Participants OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	OnabotulinumtoxinA Dose A n=313 Participants OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Percentage of Subjects With ≥2-Grade Improvement From Baseline on Both the Investigator's and Subject's Facial Wrinkle Scale (FWS) Ratings of Forehead Line Severity at Maximum Eyebrow Elevation	0.6 Percentage of Subjects Interval -0.6 to 1.9	45.6 Percentage of Subjects Interval 40.1 to 51.1	53.0 Percentage of Subjects Interval 47.5 to 58.6

SECONDARY outcome

Timeframe: Day 30

Population: Intent-to-Treat: all randomized subjects with a score of "none" and "mild" on the FWS at maximum eyebrow elevation

The Investigator assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with a score of "none" and "mild" are reported.

Outcome measures

Outcome measures
Measure	Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A n=156 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.	OnabotulinumtoxinA Dose B n=318 Participants OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	OnabotulinumtoxinA Dose A n=313 Participants OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation	3.8 Percentage of Subjects Interval 0.8 to 6.9	90.3 Percentage of Subjects Interval 87.0 to 93.5	94.9 Percentage of Subjects Interval 92.4 to 97.3

SECONDARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-Treat: all randomized subjects with at least a 1-grade improvement assessed by the Investigator on the FWS at rest

The Investigator assessed the severity of the subject's forehead lines at rest using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 1-grade improvement assessed by the Investigator are reported.

Outcome measures

Outcome measures
Measure	Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A n=150 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.	OnabotulinumtoxinA Dose B n=310 Participants OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	OnabotulinumtoxinA Dose A n=309 Participants OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest	18.7 Percentage of Subjects Interval 12.4 to 24.9	85.2 Percentage of Subjects Interval 81.2 to 89.1	84.8 Percentage of Subjects Interval 80.8 to 88.8

SECONDARY outcome

Timeframe: Day 60

Population: Intent-to-Treat: all randomized subjects with data reported at this time point

The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. Item 5 on the FLSQ asks "How satisfied are you with the effect your treatment had on your facial lines?" Responses included: very satisfied, mostly satisfied, neither satisfied or dissatisfied, mostly dissatisfied, or very dissatisfied. The percentage of subjects reporting a score of mostly satisfied or very satisfied with treatment are reported.

Outcome measures

Outcome measures
Measure	Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A n=155 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.	OnabotulinumtoxinA Dose B n=317 Participants OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	OnabotulinumtoxinA Dose A n=313 Participants OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5	3.2 Percentage of Subjects Interval 0.4 to 6.0	81.4 Percentage of Subjects Interval 77.1 to 85.7	87.9 Percentage of Subjects Interval 84.2 to 91.5

SECONDARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-Treat: all randomized subjects with baseline scores ≥ 20 on the Impact Domain of the FLSQ

The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. The Impact Domain measures the subject's appearance-related and emotional impacts of treatment and is composed of 5 questions with a possible range of scores from 0 (worst) to 100 (best), using a transformed scale. Only subjects with baseline scores ≥ 20 are included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A n=152 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.	OnabotulinumtoxinA Dose B n=310 Participants OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	OnabotulinumtoxinA Dose A n=301 Participants OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points	19.7 Percentage of Subjects Interval 13.4 to 26.1	61.0 Percentage of Subjects Interval 55.5 to 66.4	76.1 Percentage of Subjects Interval 71.3 to 80.9

SECONDARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-Treat: all randomized subjects with baseline scores ≥ 3 on Item 4 of the FLO-11

The FLO-11 assess the subject's psychological and appearance-related impacts associated with facial lines. Item 4 is "I look older than my actual age because of my facial lines" with a range of possible scores from 0 = not at all to 10 = very much. Only subjects with baseline scores ≥ 3 are included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A n=141 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.	OnabotulinumtoxinA Dose B n=285 Participants OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	OnabotulinumtoxinA Dose A n=288 Participants OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire©	9.9 Percentage of Subjects Interval 5.0 to 14.9	66.7 Percentage of Subjects Interval 61.2 to 72.1	77.1 Percentage of Subjects Interval 72.2 to 81.9

SECONDARY outcome

Timeframe: 12 Months

Population: Intent-to-Treat: all randomized subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation

Time to retreatment eligibility is defined as the number of days from treatment cycle 1 injection to the return to an Investigator FWS rating of moderate or severe at maximum eyebrow elevation. The FWS is a 4-grade scale, where 0=none, 1=mild, 2=moderate, and 3=severe. Only subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation on Day 30 are included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A n=1 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.	OnabotulinumtoxinA Dose B n=143 Participants OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	OnabotulinumtoxinA Dose A n=161 Participants OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Time to Retreatment Eligibility	64.0 Days Standard Deviation NA One incidence; therefore, SD not applicable	120.0 Days Standard Deviation 46.4	126.0 Days Standard Deviation 53.7

Adverse Events

Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

OnabotulinumtoxinA Dose B

Serious events: 7 serious events

Other events: 90 other events

Deaths: 0 deaths

OnabotulinumtoxinA Dose A

Serious events: 16 serious events

Other events: 198 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A n=156 participants at risk Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A into the protocol-specified areas.	OnabotulinumtoxinA Dose B n=318 participants at risk OnabotulinumtoxinA Dose B injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	OnabotulinumtoxinA Dose A n=746 participants at risk OnabotulinumtoxinA Dose A injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
General disorders Injection site bruising	3.2% 5/156 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.	8.2% 26/318 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.	6.3% 47/746 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.
General disorders Injection site haematoma	1.9% 3/156 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.	5.0% 16/318 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.	4.6% 34/746 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.
Infections and infestations Nasopharyngitis	3.2% 5/156 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.	5.7% 18/318 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.	6.4% 48/746 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.
Nervous system disorders Headache	5.1% 8/156 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.	9.4% 30/318 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.	9.2% 69/746 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess AEs and SAEs. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA Dose A in Period 2 are included in the onabotulinumtoxinA Dose A group for the Safety analysis.

Additional Information

Tanya Brandstetter

Allergan, Inc

Phone: 714-246-2567

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER