Moderate to Severe Glabellar Frown LinesPhase 3NCT00770029

IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Glabellar Frown Lines No. 2

A Phase 3 study testing IncobotulinumtoxinA (Xeomin) (20 Units) in people with Moderate to Severe Glabellar Frown Lines, run by Merz Pharmaceuticals GmbH at 8 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Moderate to Severe Glabellar Frown Lines
What is being tested?: IncobotulinumtoxinA (Xeomin) (20 Units)
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 276 participants
Where: 8 sitesin 2 countries
Study dates: Oct 2008to Jun 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age 18 or over
Moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on Facial Wrinkle Scale as assessed by investigator's rating: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe'
Moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on Facial Wrinkle Scale as assessed by patient's assessment: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe'
Stable medical condition

Who cannot join

Previous treatment with Botulinum toxin of any serotype in the glabellar area within the last 8 month
Previous treatment with any facial aesthetic procedure (e.g. injection with biodegradable fillers, chemical peeling, photo rejuvenation) in the glabellar area within the last 12 month
Previous insertion of permanent material in the glabellar area (regardless of the time between previous treatment and this study)
Planned treatment with Botulinum toxin of any serotype in any other body region during the study period
Any surgery in the glabellar area including surgical removal of the corrugator, procerus, or depressor supercilii muscles or a combination of these, or scars in the glabellar area and the surrounding areas (including eye brow)
Any other planned facial aesthetic procedure during the trial period

Show all 10Show fewer

Inability to substantially lessen glabellar frown lines even by physically spreading them apart
Marked facial asymmetry or ptosis of eyelid and/or eyebrow
History of facial nerve palsy
Any infection in the area of the injection sites

Trial locations and contacts

8 sites in 2 countries.

Country

City, postcode or hospital

8 sites in 2 countries

United States5 sites

SkinCare Physicians of Chestnut Hill
Chestnut Hill, Massachusetts, 02467
Skin Care Center
Los Angeles, California, 90069
Coleman William
Meatrie, Louisiana, 70006
Tennessee Clinical Research Center
Nashville, Tennessee, 37215
Flynn Consulting PLLC
Raleigh, North Carolina, 27608

Other trials in United States

Canada3 sites

Solish Nowell
Toronto, Ontario, M5R 3N8
Aesthetic Facial Ophtalmology
Vancouver, British Columbia, V5Z 4E1
Carruthers Clinical Research
Vancouver, British Columbia, V5Z 4E1

Other trials in Canada

About this study

Official title: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Investigate the Efficacy and Safety of IncobotulinumtoxinA (Xeomin), Free of Complexing Proteins, in the Treatment of Glabellar Frown Lines. No. 2

The study objective was to show the superior efficacy of IncobotulinumtoxinA (Xeomin) over placebo by evaluation of treatment success analyzing the investigator's rating on the Facial Wrinkle Scale and the patient's assessment on a 4-point scale. 255 female and male patients with moderate to severe glabellar frown lines to be randomized in a 2:1 ratio to receive one injection of IncobotulinumtoxinA (Xeomin) or placebo and will be followed up until day 120.

Read the detailed description

The study was a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter phase 3 clinical trial. Approximately 285 females and males with moderate to severe glabellar frown lines at maximum frown were to be screened during a screening period of four months in order to randomize approximately 255 subjects into one treatment and one placebo group at a ratio of 2 : 1. After the single injection treatment with a total dose of 20 Units IncobotulinumtoxinA (Xeomin) or corresponding placebo, the subjects were observed over 120 days. During the study participation the subjects performed seven visits.

Eight (8) sites in the United States and Canada participated in this trial. The study was led by one Lead PI and a Co-Lead PI who was assisting the Lead PI. The role of the Lead PI and the Co-Lead PI was executed by one of the PIs of this study, respectively. The PI at each site was a medical doctor who was experienced in aesthetic dermatology, i.e. who had several years (>=2 years) of experience in treatment of glabellar frown lines with BTX-A preparations. The PI was the person who led the team at one trial site and who was responsible for the conduct of the clinical trial at the site. The sub-investigator was a member of the team designated by the PI to perform important trial-related decisions. A maximum number of two sub-investigators could be authorized for injection and rating if necessary. At each site, ideally one investigator was to inject and rate all subjects. Injecting and rating sub-investigators had to be medical doctors with several years of experience in treatment of glabellar frown lines with BTX-A preparations. A subject had to be rated by the same investigator at all visits. Another phase 3 trial MRZ 60201-0741/1 (NCT00770211) with design and endpoints identical to those in this trial was performed in order to compare efficacy and safety results with a second study population.

Conditions: Moderate to Severe Glabellar Frown Lines
Being tested: IncobotulinumtoxinA (Xeomin) (20 Units), Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IncobotulinumtoxinA (Xeomin) (20 Units)Drug
Also called IncobotulinumtoxinA (Xeomin), also known as 'NT 201' or 'Botulinum toxin type A (150 kD), free from complexing proteins' (20 Units)
The treatment will be administered only once at day 0 at five injection sites in the glabellar area. The total dose of 20 Units IncobotulinumtoxinA (Xeomin) is reconstituted in a total injection volume of 0.5 mL that is to be injected to the five sites in equal aliquots of 0.1 mL.
PlaceboDrug
The treatment will be administered only once at day 0 at five injection sites in the glabellar area. Volume of Placebo equivalent to IncobotulinumtoxinA (Xeomin).

Study groups in NCT00770029
Study group	Role	What they receive
IncobotulinumtoxinA (Xeomin) (20 Units)	Experimental	IncobotulinumtoxinA (Xeomin), also known as 'NT 201' or 'Botulinum toxin type A (150 kD), free from complexing proteins' (active ingredient: Clostridium Botulinum neurotoxin type A free from complexing proteins) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% sodium chloride (NaCl), 20 units, total volume 0.5 mL, mode of administration: intramuscular injection Receives: Drug: IncobotulinumtoxinA (Xeomin) (20 Units)
Placebo	Placebo comparator	Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl, corresponding to total placebo volume 0.5 mL; mode of administration: intramuscular injection Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Composite Endpoint Treatment Success (CETS) Constituted by 2 Variables: 2-point Responders at Maximum Frown (Frown as Much as Possible) at Day 30 by Investigator's Rating on Facial Wrinkle Scale (FWS) and by Patient's Assessment on 4-point Scale
Composite endpoint CETS constituted by two efficacy variables:
1. The investigator's assessment on the four-point FWS: none = 0, mild = 1, moderate = 2, severe = 3.
2. Patient's assessment on the 4-point scale in comparison to sample photos: 0 = No muscle action at all; 1 = Some even slight muscle action possible i.e. visible furrows; 2 = Moderately strong muscle action possible i.e. visible muscle bulges; 3 = Strong muscle action possible which may cause local pallor.
A subject was a responder only if a 2-point improvement compared to baseline occurred simultaneously for both variables.
Measured: Baseline to Day 30

Secondary outcomes (4)

Responders at Rest at Day 30 by Investigator's Rating on FWS.
The investigator's assessment at rest (no muscle action in the face, no frown at all) on the four-point FWS: none = 0, mild = 1, moderate = 2, severe = 3. A responder was defined as a subject with a rating of none = 0 or mild = 1.
Measured: Baseline to Day 30
1-point Responders at Rest at Day 30 by Patient's Assessment on 4-point Scale.
Patient's assessment at rest (no muscle action in the face, no frown at all) on the 4-point scale in comparison to sample photos: 0 = No visible vertical line(s) at all (i.e. no visible upright line); 1 = Slightly visible vertical line(s) (i.e. slightly visible upright line); 2 = Moderate vertical line(s) with depression (i.e. upright line with deepening); 3 = Deep vertical line(s) and depression which cannot be effaced by spreading (i.e. cannot be smoothed out).
A subject was a responder if a 1-point improvement occurred compared to baseline.
Measured: Baseline to Day 30
Responders at Maximum Frown at Day 30 by Investigator's Rating on FWS.
The investigator's assessment at maximum frown (frown as much as possible) on the four-point FWS: none = 0, mild = 1, moderate = 2, severe = 3. A responder was defined as a subject with a rating of none = 0 or mild = 1.
Measured: Baseline to Day 30
1-point Responders at Maximum Frown at Day 30 by Patient's Assessment on 4-point Scale.
Patient's assessment at maximum frown (frown as much as possible) on the 4-point scale in comparison to sample photos: 0 = No muscle action at all; 1 = Some even slight muscle action possible i.e. visible furrows; 2 = Moderately strong muscle action possible i.e. visible muscle bulges; 3 = Strong muscle action possible which may cause local pallor.
A subject was a responder if a 1-point improvement occurred compared to baseline.
Measured: Baseline to Day 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2008Jun 2009

First posted9 Oct 2008 (estimated)
Study startOct 2008
Primary completionMar 2009
Study completionJun 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Moderate to Severe Glabellar Frown LinesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 276 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00770029
Sponsor's protocol ID: MRZ 60201 - 0724 / 1
Status last verified: Feb 2013
First submitted: 8 Oct 2008
Last updated: 27 Feb 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Carruthers A, Carruthers J, Coleman WP 3rd, Donofrio L, Flynn T, Gold M, Heinz M, Harrington L, Jones D, McDaniel D, Rohrer T, Schlobe A, Solish N, Weiss RA. Multicenter, randomized, phase III study of a single dose of incobotulinumtoxinA, free from complexing proteins, in the treatment of glabellar frown lines. Dermatol Surg. 2013 Apr;39(4):551-8. doi: 10.1111/dsu.12100. Epub 2013 Feb 4.
PubMed 23379292

Study at a glance

From the registry record, last updated by the sponsor on 27 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Investigate the Efficacy and Safety of IncobotulinumtoxinA (Xeomin), Free of Complexing Proteins, in the Treatment of Glabellar Frown Lines. No. 2
ClinicalTrials.gov ID: NCT00770029
Acronym / sponsor ID: MRZ 60201 - 0724 / 1
Conditions: Moderate to Severe Glabellar Frown Lines
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 276 participants (actual)
Lead sponsor: Merz Pharmaceuticals GmbHIndustry (pharma, biotech, devices)
Study start: Oct 2008
Primary completion: Mar 2009 (actual)
Study completion: Jun 2009 (actual)
First posted: 9 Oct 2008 (estimated)
Results: Posted 13 Sep 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
IncobotulinumtoxinA (Xeomin) (20 Units)	Experimental	Drug: IncobotulinumtoxinA (Xeomin) (20 Units)IncobotulinumtoxinA (Xeomin), also known as 'NT 201' or 'Botulinum toxin type A (150 kD), free from complexing proteins' (active ingredient: Clostridium Botulinum neurotoxin type A free from complexing proteins) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% sodium chloride (NaCl), 20 units, total volume 0.5 mL, mode of administration: intramuscular injection
Placebo	Placebo comparator	Drug: PlaceboPlacebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl, corresponding to total placebo volume 0.5 mL; mode of administration: intramuscular injection

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Age 18 or over
Moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on Facial Wrinkle Scale as assessed by investigator's rating: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe'
Moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on Facial Wrinkle Scale as assessed by patient's assessment: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe'
Stable medical condition

Key exclusion criteria (10 listed)

Previous treatment with Botulinum toxin of any serotype in the glabellar area within the last 8 month
Previous treatment with any facial aesthetic procedure (e.g. injection with biodegradable fillers, chemical peeling, photo rejuvenation) in the glabellar area within the last 12 month
Previous insertion of permanent material in the glabellar area (regardless of the time between previous treatment and this study)
Planned treatment with Botulinum toxin of any serotype in any other body region during the study period
Any surgery in the glabellar area including surgical removal of the corrugator, procerus, or depressor supercilii muscles or a combination of these, or scars in the glabellar area and the surrounding areas (including eye brow)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IncobotulinumtoxinA (Xeomin) (20 Units)Also: IncobotulinumtoxinA (Xeomin), also known as 'NT 201' or 'Botulinum toxin type A (150 kD), free from complexing proteins' (20 Units)The treatment will be administered only once at day 0 at five injection sites in the glabellar area. The total dose of 20 Units IncobotulinumtoxinA (Xeomin) is reconstituted in a total injection volume of 0.5 mL that is to be injected to the five sites in equal aliquots of 0.1 mL.	Drug	IncobotulinumtoxinA (Xeomin) (20 Units)
PlaceboThe treatment will be administered only once at day 0 at five injection sites in the glabellar area. Volume of Placebo equivalent to IncobotulinumtoxinA (Xeomin).	Drug	Placebo

Primary outcome

Composite Endpoint Treatment Success (CETS) Constituted by 2 Variables: 2-point Responders at Maximum Frown (Frown as Much as Possible) at Day 30 by Investigator's Rating on Facial Wrinkle Scale (FWS) and by Patient's Assessment on 4-point Scale
Time frame: Baseline to Day 30
Composite endpoint CETS constituted by two efficacy variables: 1. The investigator's assessment on the four-point FWS: none = 0, mild = 1, moderate = 2, severe = 3. 2. Patient's assessment on the 4-point scale in comparison to sample photos: 0 = No muscle action at all; 1 = Some even slight muscle action possible i.e. visible furrows; 2 = Moderately strong muscle action possible i.e. visible muscle bulges; 3 = Strong muscle action possible which may cause local pallor. A subject was a responder only if a 2-point improvement compared to baseline occurred simultaneously for both variables.

4 secondary outcomes

Responders at Rest at Day 30 by Investigator's Rating on FWS.
Time frame: Baseline to Day 30
1-point Responders at Rest at Day 30 by Patient's Assessment on 4-point Scale.
Time frame: Baseline to Day 30
Responders at Maximum Frown at Day 30 by Investigator's Rating on FWS.
Time frame: Baseline to Day 30
1-point Responders at Maximum Frown at Day 30 by Patient's Assessment on 4-point Scale.
Time frame: Baseline to Day 30

Results and safety

Results posted to the registry on 13 Sep 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
IncobotulinumtoxinA (Xeomin) (20 Units)	184	178
Placebo	92	89

Primary outcome: Composite Endpoint Treatment Success (CETS) Constituted by 2 Variables: 2-point Responders at Maximum Frown (Frown as Much as Possible) at Day 30 by Investigator's Rating on Facial Wrinkle Scale (FWS) and by Patient's Assessment on 4-point Scale

Time frame: Baseline to Day 30. Number. Unit: Participants

Measure	IncobotulinumtoxinA (Xeomin) (20 Units) n = 184	Placebo n = 92
Value	111	0

IncobotulinumtoxinA (Xeomin) (20 Units) vs Placebo: Difference response rate: 0.60 (95% CI 0.52 to 0.68), p <0.0001, Fisher Exact

Population analysed: Full Analysis Set (FAS): All randomized subjects treated with study medication. Missing values were imputed by the evaluations made at Day 7 according to the LOCF (last observation carried forward). If no ratings for Day 7 were available values were set to 'no 2-point responder'.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: All SAEs/AEs after injection were reported. All subjects experiencing SAEs/AEs were to be monitored until AE was resolved or stabilized or until a plausible explanation for the cause of the event had been found.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
IncobotulinumtoxinA (Xeomin) (20 Units)	1 of 184 (0.5%)	32 of 184 (17.4%)	Not reported
Placebo	1 of 92 (1.1%)	15 of 92 (16.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 23379292Carruthers A, Carruthers J, Coleman WP 3rd, Donofrio L, Flynn T, Gold M, Heinz M, Harrington L, Jones D, McDaniel D, Rohrer T, Schlobe A, Solish N, Weiss RA. Multicenter, randomized, phase III study of a single dose of incobotulinumtoxinA, free from complexing proteins, in the treatment of glabellar frown lines. Dermatol Surg. 2013 Apr;39(4):551-8. doi: 10.1111/dsu.12100. Epub 2013 Feb 4.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Alastair Carruthers, MD principal investigator

Jean Carruthers, MD principal investigator

8 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing IncobotulinumtoxinA (Xeomin) (20 Units) in people with Moderate to Severe Glabellar Frown Lines, run by Merz Pharmaceuticals GmbH at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite Endpoint Treatment Success (CETS) Constituted by 2 Variables: 2-point Responders at Maximum Frown (Frown as Much as Possible) at Day 30 by Investigator's Rating on Facial Wrinkle Scale (FWS) and by Patient's Assessment on 4-point Scale (time frame: Baseline to Day 30). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00770029, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2013.