Trial Outcomes & Findings for Safety and Pharmacokinetics of a Single Dose of CCH (3.36 mg) in Subjects With EFP (NCT NCT03675685)

Last Updated: 2020-10-06

Results Overview

Determine if there is systemic exposure following a subcutaneous single dose of Collagenase clostridium histolyticum (CCH) (3.36 mg) as 12 injections per quadrant in 4 quadrants concurrently (0.84 mg per quadrant) in adult women with Edematous Fibrosclerotic Panniculopathy (EFP). There were no quantifiable levels of plasma AUX-I or AUX-II observed at any collection time point following subcutaneous injection of EN3835. As a result, no pharmacokinetic (PK) parameters were calculated.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

12 participants

Primary outcome timeframe

Day 1 to Day 22

Results posted on

2020-10-06

Participant Flow

Participant milestones

Participant milestones
Measure	CCH (Collagenase Clostridium Histolyticum) CCH (collagenase clostridium histolyticum): A single dose of 3.36 mg of CCH will be administered as subcutaneous injections (CCH 0.84 mg) per quadrant concurrently in 4 quadrants. A quadrant is defined as one of the following: left buttock, right buttock, left posterolateral thigh, or right posterolateral thigh.
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Pharmacokinetics of a Single Dose of CCH (3.36 mg) in Subjects With EFP

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CCH (Collagenase Clostridium Histolyticum) n=12 Participants CCH (collagenase clostridium histolyticum): A single dose of 3.36 mg of CCH will be administered as subcutaneous injections (CCH 0.84 mg) per quadrant concurrently in 4 quadrants. A quadrant is defined as one of the following: left buttock, right buttock, left posterolateral thigh, or right posterolateral thigh.
Age, Continuous	49.3 years STANDARD_DEVIATION 10.19 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Body Mass Index (BMI)	29.94 (kg/m^2) STANDARD_DEVIATION 3.574 • n=5 Participants
Skin Category (Fitzpatrick Scale) I (Pale White)	0 Participants n=5 Participants
Skin Category (Fitzpatrick Scale) II (Fair)	1 Participants n=5 Participants
Skin Category (Fitzpatrick Scale) III (Darker White)	4 Participants n=5 Participants
Skin Category (Fitzpatrick Scale) IV (Light Brown)	3 Participants n=5 Participants
Skin Category (Fitzpatrick Scale) V (Brown)	1 Participants n=5 Participants
Skin Category (Fitzpatrick Scale) VI (Dark Brown or Black)	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 22

Population: Pharmacokinetic Population

Outcome measures

Outcome measures
Measure	CCH (Collagenase Clostridium Histolyticum) n=12 Participants CCH (collagenase clostridium histolyticum): A single dose of 3.36 mg of CCH will be administered as subcutaneous injections (CCH 0.84 mg) per quadrant concurrently in 4 quadrants. A quadrant is defined as one of the following: left buttock, right buttock, left posterolateral thigh, or right posterolateral thigh.	Right Buttock CCH 0.84 mg/Area, 3.36 mg Total	Left Thigh CCH 0.84 mg/Area, 3.36 mg Total	Right Thigh CCH 0.84 mg/Area, 3.36 mg Total
Plasma AUX-I and AUX-II Concentrations	NA mmol/L Standard Deviation NA There were no quantifiable levels of plasma AUX-I or AUX-II observed at any collection time point following subcutaneous injection of EN3835- As a result, no Pharmacokinetic (PK) parameters were calculated.	—	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 22

Population: Cellulite Severity Population

Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) scores for each quadrant are based on the investigator's CR-PCSS evaluation done at the Screening visit (Baseline) and at End of Study (Day 22). CR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe). Negative change reflects an improvement in cellulite severity; positive change reflects a worsening in cellulite severity.

Outcome measures

Outcome measures
Measure	CCH (Collagenase Clostridium Histolyticum) n=11 Participants CCH (collagenase clostridium histolyticum): A single dose of 3.36 mg of CCH will be administered as subcutaneous injections (CCH 0.84 mg) per quadrant concurrently in 4 quadrants. A quadrant is defined as one of the following: left buttock, right buttock, left posterolateral thigh, or right posterolateral thigh.	Right Buttock n=11 Participants CCH 0.84 mg/Area, 3.36 mg Total	Left Thigh n=11 Participants CCH 0.84 mg/Area, 3.36 mg Total	Right Thigh n=11 Participants CCH 0.84 mg/Area, 3.36 mg Total
Investigator CR-PCSS Rating Screening (Baseline) · None (0)	0 Participants	0 Participants	0 Participants	0 Participants
Investigator CR-PCSS Rating Screening (Baseline) · Almost None (1)	0 Participants	0 Participants	0 Participants	0 Participants
Investigator CR-PCSS Rating Screening (Baseline) · Mild (2)	6 Participants	4 Participants	8 Participants	8 Participants
Investigator CR-PCSS Rating Screening (Baseline) · Moderate (3)	4 Participants	6 Participants	3 Participants	3 Participants
Investigator CR-PCSS Rating Screening (Baseline) · Severe (4)	1 Participants	1 Participants	0 Participants	0 Participants
Investigator CR-PCSS Rating Day 22 (End of Study) · None (0)	0 Participants	0 Participants	0 Participants	0 Participants
Investigator CR-PCSS Rating Day 22 (End of Study) · Almost None (1)	1 Participants	2 Participants	5 Participants	5 Participants
Investigator CR-PCSS Rating Day 22 (End of Study) · Mild (2)	7 Participants	6 Participants	5 Participants	4 Participants
Investigator CR-PCSS Rating Day 22 (End of Study) · Moderate (3)	3 Participants	1 Participants	1 Participants	2 Participants
Investigator CR-PCSS Rating Day 22 (End of Study) · Severe (4)	0 Participants	2 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 22

Population: Cellulite Severity Population

Change from Baseline (Day 22 - Baseline). Baseline Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) scores for each quadrant are based on the investigator's CR-PCSS evaluation done at the Screening visit. CR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe). Negative change reflects an improvement in cellulite severity; positive change reflects a worsening in cellulite severity.

Outcome measures

Outcome measures
Measure	CCH (Collagenase Clostridium Histolyticum) n=11 Participants CCH (collagenase clostridium histolyticum): A single dose of 3.36 mg of CCH will be administered as subcutaneous injections (CCH 0.84 mg) per quadrant concurrently in 4 quadrants. A quadrant is defined as one of the following: left buttock, right buttock, left posterolateral thigh, or right posterolateral thigh.	Right Buttock n=11 Participants CCH 0.84 mg/Area, 3.36 mg Total	Left Thigh n=11 Participants CCH 0.84 mg/Area, 3.36 mg Total	Right Thigh n=11 Participants CCH 0.84 mg/Area, 3.36 mg Total
Investigator CR-PCSS Change From Baseline +2	0 Participants	0 Participants	0 Participants	0 Participants
Investigator CR-PCSS Change From Baseline -3	0 Participants	0 Participants	0 Participants	0 Participants
Investigator CR-PCSS Change From Baseline -2	0 Participants	1 Participants	1 Participants	0 Participants
Investigator CR-PCSS Change From Baseline -1	5 Participants	4 Participants	5 Participants	7 Participants
Investigator CR-PCSS Change From Baseline 0	5 Participants	5 Participants	5 Participants	3 Participants
Investigator CR-PCSS Change From Baseline +1	1 Participants	1 Participants	0 Participants	1 Participants
Investigator CR-PCSS Change From Baseline -4	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 22

Population: Cellulite Severity Population

Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) scores for each quadrant are based on the investigator's CR-PCSS evaluation at the end of study. CR-PCSS is a 5-level scale ranging from "0" (None) to "4" (Severe). A 2-point responder is a participant with a reduction of cellulite severity by at least 2 severity levels from baseline to end of study (i.e., change from baseline CR-PCSS rating of -2, -3, or -4). A 1-point responder is a participant with a reduction of cellulite severity by at least 1 severity level from baseline to end of study (i.e., change from baseline CR-PCSS rating of -1, -2, -3, or -4).

Outcome measures

Outcome measures
Measure	CCH (Collagenase Clostridium Histolyticum) n=11 Participants CCH (collagenase clostridium histolyticum): A single dose of 3.36 mg of CCH will be administered as subcutaneous injections (CCH 0.84 mg) per quadrant concurrently in 4 quadrants. A quadrant is defined as one of the following: left buttock, right buttock, left posterolateral thigh, or right posterolateral thigh.	Right Buttock n=11 Participants CCH 0.84 mg/Area, 3.36 mg Total	Left Thigh n=11 Participants CCH 0.84 mg/Area, 3.36 mg Total	Right Thigh n=11 Participants CCH 0.84 mg/Area, 3.36 mg Total
Investigator CR-PCSS Responder Analysis at End of Study 2-point Responder · Yes	0 Participants	1 Participants	1 Participants	0 Participants
Investigator CR-PCSS Responder Analysis at End of Study 2-point Responder · No	11 Participants	10 Participants	10 Participants	11 Participants
Investigator CR-PCSS Responder Analysis at End of Study 1-point Responder · Yes	5 Participants	5 Participants	6 Participants	7 Participants
Investigator CR-PCSS Responder Analysis at End of Study 1-point Responder · No	6 Participants	6 Participants	5 Participants	4 Participants

Adverse Events

CCH (Collagenase Clostridium Histolyticum)

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	CCH (Collagenase Clostridium Histolyticum) n=12 participants at risk CCH (collagenase clostridium histolyticum): A single dose of 3.36 mg of CCH will be administered as subcutaneous injections (CCH 0.84 mg) per quadrant concurrently in 4 quadrants. A quadrant is defined as one of the following: left buttock, right buttock, left posterolateral thigh, or right posterolateral thigh.
General disorders Injection site bruising	100.0% 12/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
General disorders Injection site pain	100.0% 12/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
General disorders Injection site oedema	33.3% 4/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
General disorders Injection site swelling	16.7% 2/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
General disorders Chills	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
General disorders Injection site erythema	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
General disorders Injection site nodule	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
General disorders Injection site pruritus	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
General disorders Injection site warmth	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
General disorders Pyrexia	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
Nervous system disorders Headache	16.7% 2/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
Nervous system disorders Burning sensation	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
Nervous system disorders Dizziness	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
Nervous system disorders Drug withdrawal headache	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
Nervous system disorders Presyncope	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
Gastrointestinal disorders Dyspepsia	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
Infections and infestations Bronchitis	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
Injury, poisoning and procedural complications Contusion	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
Musculoskeletal and connective tissue disorders Muscle spasms	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.
Vascular disorders Hot flush	8.3% 1/12 • All (serious and nonserious) AEs, from Day 1 up to Day 22 All (serious and nonserious) AEs, whether elicited or observed during study visits or spontaneously reported by the participant, including events that occurred from the time the participant signed the study-specific consent form until completion of or discharge from the study.

Additional Information

Saji Vijayan, MBBS

Endo Pharmaceuticals

Phone: 800-462-3636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place