Trial Outcomes & Findings for A Safety and Efficacy Study of OnabotulinumtoxinA in Forehead and Glabellar Facial Rhytides (NCT NCT02261467)

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

421 participants

Primary outcome timeframe

Baseline, Day 30

Results posted on

2019-01-08

Participant Flow

A total of 421 subjects were enrolled in the study, of these, 30 subjects were excluded from the data analyses at one site. The participant flow reflects all subjects included in the data analyses.

Subjects were randomized to either placebo or onabotulinumtoxinA in Period 1. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are also included in the onabotulinumtoxinA group for the Safety analysis.

Participant milestones

Participant milestones
Measure	Placebo Followed by OnabotulinumtoxinA in Period 2 Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA OnabotulinumtoxinA injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Overall Study STARTED	101	290
Overall Study COMPLETED	80	253
Overall Study NOT COMPLETED	21	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Followed by OnabotulinumtoxinA in Period 2 Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA OnabotulinumtoxinA injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Overall Study Enrolled in Error	1	0
Overall Study Protocol Violation	0	1
Overall Study Personal Reasons	17	22
Overall Study Lost to Follow-up	2	13
Overall Study Adverse Event	1	1

Baseline Characteristics

A Safety and Efficacy Study of OnabotulinumtoxinA in Forehead and Glabellar Facial Rhytides

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Followed by OnabotulinumtoxinA in Period 2 n=101 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA n=290 Participants OnabotulinumtoxinA injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	Total n=391 Participants Total of all reporting groups
Age, Customized <65 years	101 Participants n=5 Participants	281 Participants n=7 Participants	382 Participants n=5 Participants
Age, Customized >=65 years	0 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Female	87 Participants n=5 Participants	249 Participants n=7 Participants	336 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	41 Participants n=7 Participants	55 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-Treat: all randomized subjects

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.

Outcome measures

Outcome measures
Measure	Placebo Followed by OnabotulinumtoxinA in Period 2 n=101 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA n=290 Participants OnabotulinumtoxinA 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	0.0 Percentage of Subjects Zero incidences; therefore, CI not applicable	61.4 Percentage of Subjects Interval 55.8 to 67.0

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 Followed by OnabotulinumtoxinA in Period 2 n=101 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA n=290 Participants OnabotulinumtoxinA 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	2.0 Percentage of Subjects Interval -0.7 to 4.7	94.1 Percentage of Subjects Interval 91.4 to 96.8

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 Followed by OnabotulinumtoxinA in Period 2 n=96 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA n=278 Participants OnabotulinumtoxinA 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	19.8 Percentage of Subjects Interval 11.8 to 27.8	85.6 Percentage of Subjects Interval 81.5 to 89.7

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 Followed by OnabotulinumtoxinA in Period 2 n=99 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA n=289 Participants OnabotulinumtoxinA 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	1.0 Percentage of Subjects Interval -1.0 to 3.0	90.3 Percentage of Subjects Interval 86.9 to 93.7

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 Followed by OnabotulinumtoxinA in Period 2 n=90 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA n=268 Participants OnabotulinumtoxinA 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	18.9 Percentage of Subjects Interval 10.8 to 27.0	73.9 Percentage of Subjects Interval 68.6 to 79.1

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 Followed by OnabotulinumtoxinA in Period 2 n=89 Participants Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA n=246 Participants OnabotulinumtoxinA 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©	11.2 Percentage of Subjects Interval 4.7 to 17.8	77.2 Percentage of Subjects Interval 72.0 to 82.5

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 Followed by OnabotulinumtoxinA in Period 2 Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA n=174 Participants OnabotulinumtoxinA injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Time to Retreatment Eligibility	—	119 Days Standard Deviation 52.9

Adverse Events

Placebo Followed by OnabotulinumtoxinA in Period 2

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

OnabotulinumtoxinA

Serious events: 5 serious events

Other events: 92 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo Followed by OnabotulinumtoxinA in Period 2 n=100 participants at risk Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA n=374 participants at risk OnabotulinumtoxinA injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.
Cardiac disorders Angina pectoris	0.00% 0/100 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.	0.27% 1/374 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.
Immune system disorders Anaphylactic reaction	0.00% 0/100 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.	0.27% 1/374 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/100 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.	0.27% 1/374 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.
Nervous system disorders Headache	0.00% 0/100 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.	0.27% 1/374 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.
Psychiatric disorders Depression	0.00% 0/100 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.	0.27% 1/374 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.

Other adverse events

Other adverse events
Measure	Placebo Followed by OnabotulinumtoxinA in Period 2 n=100 participants at risk Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	OnabotulinumtoxinA n=374 participants at risk OnabotulinumtoxinA 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	2.0% 2/100 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.	5.1% 19/374 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.
Infections and infestations Nasopharyngitis	3.0% 3/100 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.	8.0% 30/374 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.
Nervous system disorders Headache	7.0% 7/100 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA group for the Safety analysis.	11.5% 43/374 The Safety Population includes all subjects who received at least 1 study treatment injection and was used to assess adverse events and serious adverse events. Subjects randomized to receive placebo in Period 1 who subsequently received open-label onabotulinumtoxinA in Period 2 are included in the onabotulinumtoxinA 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