Trial Outcomes & Findings for IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Glabellar Frown Lines No. 2 (NCT NCT00770029)

NCT ID: NCT00770029

Last Updated: 2013-02-27

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 276 participants
• Primary outcome timeframe: Baseline to Day 30
• Results posted on: 2013-02-27

Participant Flow

Participant milestones

Measure	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, 20 units; mode of administration: intramuscular injection	Placebo Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin).
Overall Study STARTED	184	92
Overall Study COMPLETED	178	89
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Measure	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, 20 units; mode of administration: intramuscular injection	Placebo Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin).
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	3	3
Overall Study Adverse Event	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	IncobotulinumtoxinA (Xeomin) (20 Units) n=184 Participants 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, 20 units; mode of administration: intramuscular injection	Placebo n=92 Participants Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin).	Total n=276 Participants Total of all reporting groups
Age Continuous	46.6 years STANDARD_DEVIATION 9.87 • n=5 Participants	46.4 years STANDARD_DEVIATION 10.56 • n=7 Participants	46.6 years STANDARD_DEVIATION 10.09 • n=5 Participants
Sex: Female, Male Female	162 Participants n=5 Participants	76 Participants n=7 Participants	238 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	16 Participants n=7 Participants	38 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Day 30

Population: 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'.

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.

Outcome measures

Measure	IncobotulinumtoxinA (Xeomin) (20 Units) n=184 Participants 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, 20 units; mode of administration: intramuscular injection	Placebo n=92 Participants Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin).
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	111 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to Day 30

Population: The number and percentage of responses by treatment group will be provided for all secondary endpoints on the FAS observed cases.

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.

Outcome measures

Measure	IncobotulinumtoxinA (Xeomin) (20 Units) n=184 Participants 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, 20 units; mode of administration: intramuscular injection	Placebo n=92 Participants Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin).
Responders at Rest at Day 30 by Investigator's Rating on FWS.	123 Participants	36 Participants

SECONDARY outcome

Timeframe: Baseline to Day 30

Population: The number and percentage of responses by treatment group will be provided for all secondary endpoints on the FAS observed cases.

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.

Outcome measures

Measure	IncobotulinumtoxinA (Xeomin) (20 Units) n=184 Participants 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, 20 units; mode of administration: intramuscular injection	Placebo n=92 Participants Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin).
1-point Responders at Rest at Day 30 by Patient's Assessment on 4-point Scale.	131 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline to Day 30

Population: The number and percentage of responses by treatment group will be provided for all secondary endpoints on the FAS observed cases.

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.

Outcome measures

Measure	IncobotulinumtoxinA (Xeomin) (20 Units) n=184 Participants 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, 20 units; mode of administration: intramuscular injection	Placebo n=92 Participants Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin).
Responders at Maximum Frown at Day 30 by Investigator's Rating on FWS.	147 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to Day 30

Population: The number and percentage of responses by treatment group will be provided for all secondary endpoints on the FAS observed cases.

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.

Outcome measures

Measure	IncobotulinumtoxinA (Xeomin) (20 Units) n=184 Participants 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, 20 units; mode of administration: intramuscular injection	Placebo n=92 Participants Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin).
1-point Responders at Maximum Frown at Day 30 by Patient's Assessment on 4-point Scale.	161 Participants	9 Participants

Adverse Events

IncobotulinumtoxinA (Xeomin) (20 Units)

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	IncobotulinumtoxinA (Xeomin) (20 Units) n=184 participants at risk 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, 20 units; mode of administration: intramuscular injection	Placebo n=92 participants at risk Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin).
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/184 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.	1.1% 1/92 • Number of events 1 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/184 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.	1.1% 1/92 • Number of events 1 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.54% 1/184 • Number of events 1 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.	0.00% 0/92 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.

Other adverse events

Measure	IncobotulinumtoxinA (Xeomin) (20 Units) n=184 participants at risk 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, 20 units; mode of administration: intramuscular injection	Placebo n=92 participants at risk Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; mode of administration: same as for IncobotulinumtoxinA (Xeomin).
Infections and infestations Nasopharyngitis	5.4% 10/184 • Number of events 10 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.	5.4% 5/92 • Number of events 5 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.
Nervous system disorders Headache	7.1% 13/184 • Number of events 13 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.	6.5% 6/92 • Number of events 7 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.
Infections and infestations Sinusitis	3.3% 6/184 • Number of events 6 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.	3.3% 3/92 • Number of events 3 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.
Infections and infestations Bronchitis	2.2% 4/184 • Number of events 5 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.	0.00% 0/92 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.
Infections and infestations Influenza	0.00% 0/184 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.	2.2% 2/92 • Number of events 2 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.
Nervous system disorders Tension headache	0.00% 0/184 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.	2.2% 2/92 • Number of events 2 • 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. Data pertaining to AEs were collected during each study visit either based on the subject's spontaneous description or by investigator's inquiry or discovered in the course of examinations done during the visit. The table of 'Other Adverse Events' includes all non-serious AEs.

Additional Information

Dr. Matthias Zerm

Merz Pharmaceuticals GmbH

Phone: 0049-69-1503

Email: matthias.zerm@merz.de

Results disclosure agreements

• Principal investigator is a sponsor employee No results to be published without written agreement by sponsor; manuscripts to be sent to sponsor at least 6 wks before submission. Sponsor to give written opinion within 30 d. Sponsor is entitled to exert influence on the contents of publications, to postpone publications up to 36 months after end of the study, and to name co-authors. In case of justified doubts of sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.
• Publication restrictions are in place

Restriction type: OTHER