NCT02261493

A Safety and Efficacy Study of OnabotulinumtoxinA in Upper Facial Rhytides

Completed Phase 3 Results posted Last updated 25 July 2017

What this trial tests

Phase 3 trial testing OnabotulinumtoxinA in Facial Rhytides in 787 participants. Completed in 20 April 2016.

Timeline

27 October 2014

Primary endpoint
3 June 2015

20 April 2016

Quick facts

Lead sponsor	Allergan
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	787
Start date	27 October 2014
Primary completion	3 June 2015
Estimated completion	20 April 2016
Sites	24 locations across Belgium, United Kingdom, United States, Germany

Drugs / interventions tested

• OnabotulinumtoxinA (ONABOTULINUMTOXINA) — full drug profile →
• Normal Saline

Conditions studied

• Facial Rhytides — all drugs for Facial Rhytides →
• Glabellar Rhytides — all drugs for Glabellar Rhytides →

Sponsor

Allergan — full company profile →

Who can join

18 and older, any sex, with Facial Rhytides or Glabellar Rhytides. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · Baseline, Day 30

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.

Group	Value	95% CI
Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A	0.6	-0.6 – 1.9
OnabotulinumtoxinA Dose B	45.6	40.1 – 51.1
OnabotulinumtoxinA Dose A	53.0	47.5 – 58.6

Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation Secondary · Day 30

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.

Group	Value	95% CI
Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A	3.8	0.8 – 6.9
OnabotulinumtoxinA Dose B	90.3	87.0 – 93.5
OnabotulinumtoxinA Dose A	94.9	92.4 – 97.3

Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest Secondary · Baseline, Day 30

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.

Group	Value	95% CI
Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A	18.7	12.4 – 24.9
OnabotulinumtoxinA Dose B	85.2	81.2 – 89.1
OnabotulinumtoxinA Dose A	84.8	80.8 – 88.8

Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5 Secondary · Day 60

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.

Group	Value	95% CI
Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A	3.2	0.4 – 6.0
OnabotulinumtoxinA Dose B	81.4	77.1 – 85.7
OnabotulinumtoxinA Dose A	87.9	84.2 – 91.5

Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points Secondary · Baseline, Day 30

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.

Group	Value	95% CI
Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A	19.7	13.4 – 26.1
OnabotulinumtoxinA Dose B	61.0	55.5 – 66.4
OnabotulinumtoxinA Dose A	76.1	71.3 – 80.9

Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire© Secondary · Baseline, Day 30

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.

Group	Value	95% CI
Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A	9.9	5.0 – 14.9
OnabotulinumtoxinA Dose B	66.7	61.2 – 72.1
OnabotulinumtoxinA Dose A	77.1	72.2 – 81.9

Time to Retreatment Eligibility Secondary · 12 Months

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.

Group	Value	95% CI
Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A	64.0	± NA
OnabotulinumtoxinA Dose B	120.0	± 46.4
OnabotulinumtoxinA Dose A	126.0	± 53.7

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo (Normal Saline) Followed by OnabotulinumtoxinA Dose A

Serious: 2/156 (1%)

Deaths: —

OnabotulinumtoxinA Dose B

Serious: 7/318 (2%)

Deaths: —

OnabotulinumtoxinA Dose A

Serious: 16/746 (2%)

Deaths: —

Serious adverse events (27 terms)

Reaction	System	Placebo (Normal Saline) Fo…	OnabotulinumtoxinA Dose B	OnabotulinumtoxinA Dose A
Cellulitis	Infections and infestations	—	—	—
Overdose	Injury, poisoning and procedural complications	—	—	—
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	—	—	—
Abdominal hernia	Gastrointestinal disorders	—	—	—
Abscess	Infections and infestations	—	—	—
Meningitis viral	Infections and infestations	—	—	—
Concussion	Injury, poisoning and procedural complications	—	—	—
Femoral neck fracture	Injury, poisoning and procedural complications	—	—	—
Fibula fracture	Injury, poisoning and procedural complications	—	—	—
Foot fracture	Injury, poisoning and procedural complications	—	—	—
Ligament rupture	Injury, poisoning and procedural complications	—	—	—
Lower limb fracture	Injury, poisoning and procedural complications	—	—	—
Post procedural inflammation	Injury, poisoning and procedural complications	—	—	—
Rib fracture	Injury, poisoning and procedural complications	—	—	—
Tibia fracture	Injury, poisoning and procedural complications	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Intervertebral disc disorder	Musculoskeletal and connective tissue disorders	—	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Large intestine benign neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Malignant melanoma stage II	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Squamous cell carcinoma of the tongue	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Neuritis	Nervous system disorders	—	—	—
Temporal lobe epilepsy	Nervous system disorders	—	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	Placebo (Normal Saline) Fo…	OnabotulinumtoxinA Dose B	OnabotulinumtoxinA Dose A
Headache	Nervous system disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Injection site bruising	General disorders	—	—	—
Injection site haematoma	General disorders	—	—	—

Most-reported serious reactions: Cellulitis, Overdose, Abortion spontaneous, Abdominal hernia, Abscess, Meningitis viral, Concussion, Femoral neck fracture.

Data from ClinicalTrials.gov NCT02261493 adverse events section.

Sponsor's own description

This is a safety and efficacy study of onabotulinumtoxinA in subjects with upper facial rhytides (forehead lines, glabellar lines, lateral canthal lines \[crow's feet lines\]).

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Neurotoxin Impurities: A Review of Threats to Efficacy.
   Park JY, Sunga O, Wanitphakdeedecha R, Frevert J. · · 2020 · cited 27× · PMID 32095419 · DOI 10.1097/gox.0000000000002627
2. OnabotulinumtoxinA Treatment for Moderate to Severe Forehead Lines: A Review.
   De Boulle K, Carruthers A, Solish N, Carruthers J, et al · · 2020 · cited 7× · PMID 32537333 · DOI 10.1097/gox.0000000000002669