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Trial record 1 of 2 for:    ACE-083 | facioscapulohumeral muscular dystrophy
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Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02927080
Recruitment Status : Terminated (Study was discontinued as it did not achieve functional secondary endpoints.)
First Posted : October 6, 2016
Results First Posted : April 22, 2021
Last Update Posted : April 22, 2021
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Facioscapulohumeral Muscular Dystrophy
Interventions Drug: ACE-083
Drug: ACE-083 or placebo
Enrollment 95
Recruitment Details First subject enrolled 22 November 2016, last subject completed 09 October 2019. The study was divided into parts; Part 1 was an open-label dose escalation study and had 6 cohorts and Part 2 was a randomized double-blind placebo controlled trial. Participants were recruited from 23 study centers in 3 countries (US, Canada and Spain).
Pre-assignment Details  
Arm/Group Title ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) Unilateral ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) Unilateral ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) Bilateral ACE-083 (Part 1, Cohort 1b) Biceps Brachii (BB) Unilateral ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) Unilateral ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) Unilateral Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Biceps Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description ACE-083 150 mg Tibialis Anterior (TA) unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 150 mg Biceps Brachii (BB) unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein Double-Blind, Placebo-Controlled Placebo TA bilaterally, once every 3 weeks for up to 9 doses. Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Double-Blind, Placebo-Controlled Placebo-BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Period Title: Overall Study
Started 6 6 6 6 7 6 15 14 15 14
Open-Label Extension From Part 2 Double Blind-Placebo Controlled [1] 0 0 0 0 0 0 14 13 14 12
Completed 6 5 6 6 6 6 7 5 12 7
Not Completed 0 1 0 0 1 0 8 9 3 7
Reason Not Completed
Withdrawal by Subject             0             0             0             0             1             0             1             1             0             2
Willingness to comply with protocol             0             0             0             0             0             0             0             0             0             1
Study terminated by Sponsor             0             0             0             0             0             0             6             7             2             3
Adverse Event             0             1             0             0             0             0             0             1             0             1
Other             0             0             0             0             0             0             1             0             1             0
[1]
Patients who completed the double-blind (DB) treatment period continued into the open-label extension (OLE) period. Patients who received ACE-083 in the DB treatment period continued to receive the same dose of ACE-083 during the OLE period, and patients who received placebo during the DB treatment period were switched to receive ACE-083, 240 mg/muscle. In the OLE period, ACE-083 was administered bilaterally in either the TA or BB muscle once every 3 weeks for approximately 6 months (8 doses).
Arm/Group Title ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) 150mg ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) 200mg ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) 200mg ACE-083 (Part 1, Cohort 1b) Biceps Brachii (BB) 150 mg ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) 200 mg ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) 240 mg Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Biceps Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) Total
Hide Arm/Group Description ACE-083 150 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 150 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein

Double-Blind, Placebo-Controlled Placebo- TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein.

Double-Blind, Placebo-Controlled Placebo- BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Total of all reporting groups
Overall Number of Baseline Participants 6 6 6 6 7 6 15 14 15 14 95
Hide Baseline Analysis Population Description
The Safety population was used for the results posting for both parts of the study. The Safety Set consists of all patients who received at least one dose of the study drug (including placebo).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 7 participants 6 participants 15 participants 14 participants 15 participants 14 participants 95 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
 100.0%
6
 100.0%
6
 100.0%
5
  83.3%
6
  85.7%
6
 100.0%
15
 100.0%
13
  92.9%
13
  86.7%
13
  92.9%
89
  93.7%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
1
  14.3%
0
   0.0%
0
   0.0%
1
   7.1%
2
  13.3%
1
   7.1%
6
   6.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 6 participants 6 participants 7 participants 6 participants 15 participants 14 participants 15 participants 14 participants 95 participants
46.7  (4.3) 43.7  (16.9) 50.7  (7.6) 52.2  (10.8) 48.3  (17.6) 41.2  (14) 41.3  (14.5) 50.9  (11.4) 46.3  (17.2) 46.7  (10.8) 46.6  (13.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 7 participants 6 participants 15 participants 14 participants 15 participants 14 participants 95 participants
Female
3
  50.0%
3
  50.0%
4
  66.7%
2
  33.3%
3
  42.9%
2
  33.3%
7
  46.7%
8
  57.1%
3
  20.0%
4
  28.6%
39
  41.1%
Male
3
  50.0%
3
  50.0%
2
  33.3%
4
  66.7%
4
  57.1%
4
  66.7%
8
  53.3%
6
  42.9%
12
  80.0%
10
  71.4%
56
  58.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 7 participants 6 participants 15 participants 14 participants 15 participants 14 participants 95 participants
Hispanic or Latino
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.1%
Not Hispanic or Latino
6
 100.0%
5
  83.3%
6
 100.0%
6
 100.0%
7
 100.0%
5
  83.3%
14
  93.3%
14
 100.0%
14
  93.3%
14
 100.0%
91
  95.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
2
   2.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 7 participants 6 participants 15 participants 14 participants 15 participants 14 participants 95 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
1
   1.1%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.1%
0
   0.0%
2
  14.3%
3
   3.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
1
   1.1%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
1
   7.1%
1
   6.7%
0
   0.0%
3
   3.2%
White
6
 100.0%
5
  83.3%
6
 100.0%
6
 100.0%
6
  85.7%
6
 100.0%
14
  93.3%
12
  85.7%
12
  80.0%
12
  85.7%
85
  89.5%
More than one race
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 7 participants 6 participants 15 participants 14 participants 15 participants 14 participants 95 participants
Canada 0 1 2 0 0 1 1 3 6 5 19
United States 6 5 4 6 7 5 9 7 6 8 63
Spain 0 0 0 0 0 0 5 4 3 1 13
1.Primary Outcome
Title Safety and Tolerability (Incidence of Adverse Events)
Hide Description The number of participants that had a least one Treatment Emergent Adverse Event for the duration of each of the respective study parts.
Time Frame From initiation of treatment to Day 106 for Part 1 and Day 190 for Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
The safety set population is all participants that received at least one dose of ACE-083 or placebo during the study.
Arm/Group Title ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) 150 mg ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) 200 mg ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) 200 mg ACE-083 (Part 1, Cohort 1b) Biceps Brachii (BB) 150 mg ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) 200 mg ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) 240 mg Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Biceps Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description:
ACE-083 150 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein.
ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 150 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein

Double-Blind, Placebo-Controlled Placebo-TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Double-Blind, Placebo-Controlled Placebo- BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 6 6 6 6 7 6 15 14 15 14
Measure Type: Count of Participants
Unit of Measure: Participants
6
 100.0%
6
 100.0%
5
  83.3%
6
 100.0%
7
 100.0%
6
 100.0%
12
  80.0%
14
 100.0%
13
  86.7%
14
 100.0%
2.Primary Outcome
Title Safety and Tolerability (Severity of Adverse Events, Grade 3 or Higher).
Hide Description The number of participants that had a least one Treatment Emergent Adverse Event with CTCAE Grade 3 or Higher for the duration of each of the respective study parts.
Time Frame From initiation of treatment to Day 106 for Part 1 and Day 190 for Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
The safety set population is all participants that received at least one dose of ACE-083 or placebo during the study.
Arm/Group Title ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) 150 mg ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) 200 mg ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) 200 mg ACE-083 (Part 1, Cohort 1b) Biceps Brachii (BB) 150 mg ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) 200 mg ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) 240 mg Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Biceps Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description:
ACE-083 150 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 150 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein

Double-Blind, Placebo-Controlled Placebo- TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Double-Blind, Placebo-Controlled Placebo- BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 6 6 6 6 7 6 15 14 15 14
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.1%
1
   6.7%
1
   7.1%
3.Primary Outcome
Title Safety and Tolerability (Severity of Adverse Events- Dose Interruption, Reduction and/or Drug Withdrawal)
Hide Description The number of participants that had a least one Treatment Emergent Adverse Event that led to dose interruption, dose reduction and/or drug withdrawn.
Time Frame From initiation of treatment to Day 106 for Part 1 and Day 190 for Part 2
Hide Outcome Measure Data
Hide Analysis Population Description
The safety set population is all participants that received at least one dose of ACE-083 or placebo during the study.
Arm/Group Title ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) 150 mg ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) 200 mg ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) 200 mg ACE-083 (Part 1, Cohort 1b ) Biceps Brachii (BB) 150 mg ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) 200 mg ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) 240 mg Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Biceps Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description:
ACE-083 150 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 150 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein

Double-Blind, Placebo-Controlled Placebo- TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Double-Blind, Placebo-Controlled Placebo- BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 6 6 6 6 7 6 15 14 15 14
Measure Type: Count of Participants
Unit of Measure: Participants
Dose interruption
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Dose reduction
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.1%
0
   0.0%
0
   0.0%
Drug Withdrawal
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.1%
4.Primary Outcome
Title Total Muscle Volume (TMV) of the Treated Muscle in Patients With FSHD Administered ACE-083 or Placebo During Part 2 (Randomized, Controlled Portion)
Hide Description Total Muscle Volume (TMV)of the treated muscle in Patients with FSHD administered ACE-083 or placebo During Part 2 (randomized, controlled portion) from Baseline to Day 190. Total Muscle volume was measured by Magnetic Resonance Imaging (MRI). MRI was performed bilaterally on the tibialis anterior and the biceps brachii on Day 1, Day Day 43, Day 106, and Day 190. Baseline and Day 190 total muscle volume, means and standard deviations are reported.
Time Frame Time Frame: From initiation of treatment to Study Visit Day 190
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Arm/Group Title Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Biceps Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description:

Double-Blind, Placebo-Controlled Placebo- TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein.

Double-Blind, Placebo-Controlled Placebo- BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 14 13 14 14
Mean (Standard Deviation)
Unit of Measure: mm3
Baseline Total Muscle Volume (TMV) Number Analyzed 14 participants 13 participants 13 participants 14 participants
79708.77  (4507.67) 85159.90  (22382.20) 104788.87  (58681.86) 89133.23  (48264.27)
Day 190 Total Muscle Volume (TMV) Number Analyzed 14 participants 13 participants 14 participants 14 participants
81761.70  (43533.71) 95739.04  (20689.98) 109489.17  (56130.61) 102131.94  (54608.84)
5.Primary Outcome
Title Percent Change of Total Muscle Volume (TMV) of the Treated Muscle in Patients With FSHD Administered ACE-083 or Placebo During Part 2 (Randomized, Controlled Portion)
Hide Description Percent Change of Total Muscle Volume (TMV)of the treated muscle in Patients with FSHD administered ACE-083 or placebo During Part 2 (randomized, controlled portion) from Baseline to Day 190. Total Muscle volume was measured by Magnetic Resonance Imaging (MRI). MRI was performed bilaterally on the tibialis anterior and the biceps brachii on Day 1, Day Day 43, Day 106, and Day 190. Percent Change from Baseline to Day 190 total muscle volume, mean and standard deviation is reported.
Time Frame Time Frame: From initiation of treatment to Study Visit Day 190
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Arm/Group Title Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Biceps Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description:

Double-Blind, Placebo-Controlled Placebo- TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein.

Double-Blind, Placebo-Controlled Placebo- BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 14 13 14 14
Mean (Standard Deviation)
Unit of Measure: percent change
5.46  (7.32) 14.20  (10.72) 1.07  (8.08) 20.41  (16.64)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part 2, DB-PC) Tibialis Anterior (TA), ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg
Comments D190 Percent change from baseline in TMV
Type of Statistical Test Superiority
Comments Percent Change in Total Muscle Volume (TMV) of the TA muscle in patients with FSHD administered ACE-083 when compared to placebo During Part 2 (randomized, controlled portion)
Statistical Test of Hypothesis P-Value 0.0138
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.54
Confidence Interval (2-Sided) 90%
3.17 to 15.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.876
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Part 2, DB-PC) Biceps Brachii (BB), ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Comments D190 Percent change from baseline in TMV
Type of Statistical Test Superiority
Comments Percent Change in Total Muscle Volume (TMV) of the BB muscle in patients with FSHD administered ACE-083 when compared to placebo During Part 2 (randomized, controlled portion)
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 16.39
Confidence Interval (2-Sided) 90%
9.75 to 23.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.032
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percent Change in Total Muscle Volume (TMV) in Muscle in Patients With FSHD Administered ACE-083 During Part 1 (Open-label, Dose-escalation Portion)
Hide Description Percent Change in Total Muscle Volume (TMV) in muscle in patients with FSHD administered ACE-083 During 1 (open-label, dose-escalation portion) from Baseline to Day 106. Total Muscle volume was measured by Magnetic Resonance Imaging (MRI). MRI was performed bilaterally on the tibialis anterior and the biceps brachii on Day 1, Day Day 43, and Day 106, change from Baseline and Day 106 reported.
Time Frame Time Frame: From initiation of treatment to Study Visit Day 106
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Arm/Group Title ACE-083 (Part 1, Cohort 1a) Tibialis Anterior (TA) 150 mg ACE-083 (Part 1, Cohort 2a) Tibialis Anterior (TA) 200mg ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) 200 mg ACE-083 (Part 1, Cohort 1b) Biceps Brachii (BB) 150 mg ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) 200 mg ACE-083 (Part 1, Cohort 3b) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description:
ACE-083 150 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 150 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Overall Number of Participants Analyzed 6 6 6 6 6 6
Mean (Standard Error)
Unit of Measure: percent change
8.1  (3.5) 18.3  (3.7) 19.7  (2.8) 8.2  (6.0) 17.1  (7.8) 16.2  (4.7)
7.Secondary Outcome
Title Absolute Change in Fat Fraction (FF) of the Muscle in Patients With FSHD Administered ACE-083 or Placebo During Part 2 (Randomized, Controlled Portion)
Hide Description Absolute change in Fat Fraction (FF) of the muscle in patients with FSHD administered ACE-083 or Placebo During Part 2 (randomized, controlled portion) from Baseline to Day 190. Absolute change in intramuscular fat fraction in the tibialis anterior and biceps brachii were measured by Magnetic Resonance Imaging (MRI). MRI was performed bilaterally on the tibialis anterior and the biceps brachii on Day 1, Day Day 43, Day 106, and Day 190, change from Baseline and Day 190 reported.
Time Frame Time Frame: From initiation of treatment to Study Visit Day 190
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Arm/Group Title Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Bicpes Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description:

Double-Blind, Placebo-Controlled Placebo-TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Double-Blind, Placebo-Controlled Placebo- BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 14 13 14 14
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-0.32  (0.888) -3.05  (0.946) 1.03  (0.955) -0.22  (0.978)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part 2, DB-PC) Tibialis Anterior (TA), ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg
Comments D190 Absolute change from baseline in FF for the TA group administered ACE-083 when compared to Placebo in part 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0359
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.73
Confidence Interval (2-Sided) 90%
-4.86 to -0.59
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.299
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Part 2, DB-PC) Bicpes Brachii (BB), ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Comments D190 Absolute change from baseline in FF for the BB group administered ACE-083 when compared to Placebo in part 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3582
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.25
Confidence Interval (2-Sided) 90%
-3.49 to 0.99
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.359
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percent Change From Baseline in Function of Tibialis Anterior, Part 2 (Randomized, Controlled Portion)
Hide Description Percent change from baseline in function of Tibialis Anterior during Part 2 assessed by: 6-minute walk test, 10 meter walk/run and 4-stair climb (ascend)
Time Frame From initiation of treatment (Study Day 1) to Study Visit Day 190
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Arm/Group Title Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg
Hide Arm/Group Description:

Double-Blind, Placebo-Controlled Placebo- TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 14 13
Least Squares Mean (Standard Error)
Unit of Measure: percent change
D190 6MWD from baseline 8.56  (2.764) 3.28  (2.937)
D190 time to complete 10mW/R from baseline -8.59  (3.351) -3.90  (3.585)
D190 4-stair ascend time from baseline -5.20  (4.065) -4.75  (4.318)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part 2, DB-PC) Tibialis Anterior (TA), ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg
Comments D190 Percent change from baseline in 6 Minute Walk Test (MWT) distance from baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1945
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.28
Confidence Interval (2-Sided) 90%
-11.97 to 1.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.068
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Part 2, DB-PC) Tibialis Anterior (TA), ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg
Comments D190 Percent change from baseline in time to complete a 10 meter walk/run
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3451
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.69
Confidence Interval (2-Sided) 90%
-3.48 to 12.86
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.968
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (Part 2, DB-PC) Tibialis Anterior (TA), ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg
Comments D190 Percent change from baseline in time to complete 4-stair climb (ascend)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9402
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.45
Confidence Interval (2-Sided) 90%
-9.47 to 10.37
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.030
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percent Change From Baseline in Strength of Biceps Brachii, Part 2, Randomized-controlled
Hide Description Elbow flexion strength measured by hand-held dynamometry (quantitative muscle testing), maximum voluntary isometric contraction (MVIC).
Time Frame From initiation of treatment (Study Day 1) to Study Visit Day 190
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Arm/Group Title Placebo (Part 2, DB-PC) Biceps Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description:

Double-Blind, Placebo-Controlled Placebo-BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 14 12
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-3.54  (10) 32.58  (10.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part 2, DB-PC) Biceps Brachii (BB), ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0183
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 36.12
Confidence Interval (2-Sided) 90%
11.78 to 60.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 14.18
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percent Change From Baseline in Performance of the Upper Limb (PUL) Mid-Level Elbow Dimension, Part 2, Randomized-controlled
Hide Description Percent Change from Baseline in Performance of the Upper Limb (PUL) Mid-Level Elbow Dimension, Part 2, Randomized-controlled, PUL from baseline to end of treatment (Day 190). The Performance of the Upper Limb is an assessment specifically designed for patients with Duchenne muscular dystrophy. The measures used in this study was a subset of the assessment. PUL was assessment by measures of high-level of movement (lifting weights of 50g, 200g, 500g and 1000g at shoulder height and above shoulder height) and mid-level movement by performing tasks with and without weights: hand to mouth with and without weights (50, 200g), hand to table, moving weights on table (100g, 200g, 500g and 1000g), lift light and heavy cans, stack light and heavy cans, remove lid from container, tearing paper).
Time Frame From initiation of treatment (Study Day 1) to Study Visit Day 190
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Arm/Group Title Placebo (Part 2, DB-PC) Biceps Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description:

Double-Blind, Placebo-Controlled Placebo- BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 14 14
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-1.19  (1.16) 1.70  (1.17)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part 2, DB-PC) Biceps Brachii (BB), ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0895
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.89
Confidence Interval (2-Sided) 90%
0.09 to 5.69
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.70
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Facioscapulohumeral Muscular Dystrophy-health Index (FSHD-HI), Patient-reported Outcome (PRO) Measures Part 2 (Randomized, Controlled Portion)- Total Score
Hide Description The facioscapulohumeral muscular dystrophy-health index (FSHD-HI) is a disease-specific patient-reported outcome (PRO) tool assessed by health-related quality of life and disease burden. The FSHD-HI questionnaire was designed to measure both overall FSHD health-related quality-of-life and 14 separate subdomains designed and based on patient interviews to measure total FSHD health-related quality-of-life, including both motor impairment and the social and emotional impact of FSHD. The 116 questions are combined into a total score, the score is transformed onto a percentage scale; with a range of 0-100, with 100 representing maximal disability, and lower scores representing decreasing disability, 0 representing no disability. The mean and standard deviation for baseline and day 190 are reported as is the absolute change from baseline to Day 190 during the randomized controlled portion of Part 2.
Time Frame Time Frame: From initiation of treatment (Study Day 1) to Study Visit Day 190
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Set: All patients enrolled/randomized in the study who received at least one dose of the study drug (includes placebo) with no major protocol violations.
Arm/Group Title Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Biceps Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description:

Double-Blind, Placebo-Controlled Placebo- TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Double-Blind, Placebo-Controlled Placebo- BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 14 13 14 14
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline FSHD-HI total score 37.65  (15.60) 45.51  (28.44) 45.52  (23.38) 25.89  (21.78)
Day 190 FSHD-HI total score 39.44  (18.76) 46.18  (29.15) 47.27  (22.73) 28.04  (27.31)
Absolute Change Day 190 from Baseline 1.79  (4.83) 0.67  (6.02) 1.75  (6.90) 2.15  (12.76)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part 2, DB-PC) Tibialis Anterior (TA), ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg
Comments Change from baseline in FSHD-HI, patient-reported outcome (PRO) measures Part 2 (Randomized, Controlled Portion)- Total Score for TA group part 2; compared to Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5661
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.98
Confidence Interval (2-Sided) 90%
-7.67 to 3.70
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.459
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Part 2, DB-PC) Biceps Brachii (BB), ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Comments Change from baseline in FSHD-HI, patient-reported outcome (PRO) measures Part 2 (Randomized, Controlled Portion)- Total Score for BB group part 2; compared to Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9760
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.11
Confidence Interval (2-Sided) 90%
-6.06 to 5.84
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.618
Estimation Comments [Not Specified]
12.Secondary Outcome
Title ACE-083 Serum Concentration Following Local Intramuscular Administration (200 mg Tibialis Anterior (TA) Bilaterally) Day 2, 24-hours After Dose
Hide Description Pharmacokinetic assessment included ACE-083 serum concentration collection and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. Timepoints that have data are reported; Day 2, 24-hours after dose is reported.
Time Frame Day 2, 24-hours after dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
Arm/Group Title ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) Bilateral)
Hide Arm/Group Description:
ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
42.03  (16.82)
13.Secondary Outcome
Title ACE-083 Serum Concentration Following Local Intramuscular Administration (200 mg Tibialis Anterior (TA) Bilaterally) Day 85, 6-hours After Dose
Hide Description Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 86, 6-hours post-dose is reported.
Time Frame Study Day 85 (6 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
Arm/Group Title ACE-083 (Part 1, Cohort 3a) Tibialis Anterior (TA) Bilateral
Hide Arm/Group Description:
ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: ng/mL
63.9  (54.31)
14.Secondary Outcome
Title ACE-083 Serum Concentration Following Local Intramuscular Administration (200 mg Biceps Brachii (BB) Unilateral) Day 1, 6-hours Post-dose
Hide Description Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 1, 6-hours post-dose, is reported.
Time Frame Study Day 1, 6-hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
Arm/Group Title ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) Unilateral
Hide Arm/Group Description:
ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
36.13  (12.7)
15.Secondary Outcome
Title ACE-083 Serum Concentration Following Local Intramuscular Administration (200 mg Biceps Brachii (BB) Unilateral) Day 85, 4-hours Post-dose
Hide Description Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported.
Time Frame Study Day 85, 4-hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
Arm/Group Title ACE-083 (Part 1, Cohort 2b) Biceps Brachii (BB) Unilateral
Hide Arm/Group Description:
ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
23.9  (2.87)
16.Secondary Outcome
Title ACE-083 Serum Concentration Following Local Intramuscular Administration (240 mg Tibialis Anterior (TA) Bilaterally) Day 2, 24- Hours Post-dose
Hide Description Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 2, 24-hours post-dose is reported.
Time Frame Day 2, 24-hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
Arm/Group Title ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Day 2, 24 Hours Post-dose
Hide Arm/Group Description:

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ng/mL
65.08  (35.4)
17.Secondary Outcome
Title ACE-083 Serum Concentration Following Local Intramuscular Administration (240 mg Tibialis Anterior (TA) Bilaterally) Day 86, 24- Hours Post-dose
Hide Description Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 86, 24-hours post-dose is reported.
Time Frame Day 86, 24-hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
Arm/Group Title ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg
Hide Arm/Group Description:

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: ng/mL
52.91  (37.74)
18.Secondary Outcome
Title ACE-083 Serum Concentration Following Local Intramuscular Administration (240 mg Biceps Brachii (BB) Bilaterally) Day 2, 24- Hours Post-dose
Hide Description Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 2, 24-hours post-dose is reported.
Time Frame Day 2, 24-hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
Arm/Group Title ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg Day 1, 2 Hours Post-dose
Hide Arm/Group Description:

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
54.8  (20.97)
19.Secondary Outcome
Title ACE-083 Serum Concentration Following Local Intramuscular Administration (240 mg Biceps Brachii (BB) Bilaterally) Day 86, 24 Hours Post-dose
Hide Description Pharmacokinetic assessment included ACE-083 serum concentration and on a dosing day had a ±15 minute window for post-dose sample collection, based on the time of the first injection. The timepoints for which data is available are reported. Day 86, 24-hours post-dose is reported.
Time Frame Day 86, 24- hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics Population: All patients who have received at least one dose of study drug and have sufficient pharmacokinetic (PK) samples collected and assayed for PK analysis
Arm/Group Title ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description:

Double-Blind, Placebo-Controlled ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ng/mL
46.87  (10.18)
Time Frame For part 1 (open-label; dose-escalation) the time frame is six months For part 2, there are two parts: randomized, double-blind, placebo-controlled and then an open-label portion- the total time frame for part 2 is fifteen months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ACE-083 (Part 1, Cohort 1a ) Tibialis Anterior (TA) 150mg ACE-083 (Part 1, Cohort 2a ) Tibialis Anterior (TA) 200mg ACE-083 (Part 1, Cohort 3a ) Tibialis Anterior (TA) 200mg ACE-083 (Part 1, Cohort 1b ) Biceps Brachii (BB) 150 mg ACE-083 (Part 1, Cohort 2b ) Biceps Brachii (BB) 200 mg ACE-083 (Part 1, Cohort 3b ) Biceps Brachii (BB) 240 mg Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Bicpes Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg ACE-083 (Part 2, Open-label) Tibialis Anterior (TA) 240 mg ACE-083 (Part 2, Open-label) Biceps Brachii (BB) 240 mg
Hide Arm/Group Description ACE-083 150 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 200 mg TA unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 200 mg TA bilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 150 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 200 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein ACE-083 240 mg BB unilaterally, once every 3 weeks for up to 5 doses. Drug: ACE-083 Recombinant fusion protein.

Double-Blind, Placebo-Controlled Placebo TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

Double-Blind, Placebo-Controlled ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

Double-Blind, Placebo-Controlled Placebo BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: Placebo Normal saline

ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 9 doses.

Drug: ACE-083 Recombinant fusion protein

ACE-083 240 mg TA bilaterally, once every 3 weeks for up to 8 doses.

Drug: ACE-083 Recombinant fusion protein

ACE-083 240 mg BB bilaterally, once every 3 weeks for up to 8 doses.

Drug: ACE-083 Recombinant fusion protein

All-Cause Mortality
ACE-083 (Part 1, Cohort 1a ) Tibialis Anterior (TA) 150mg ACE-083 (Part 1, Cohort 2a ) Tibialis Anterior (TA) 200mg ACE-083 (Part 1, Cohort 3a ) Tibialis Anterior (TA) 200mg ACE-083 (Part 1, Cohort 1b ) Biceps Brachii (BB) 150 mg ACE-083 (Part 1, Cohort 2b ) Biceps Brachii (BB) 200 mg ACE-083 (Part 1, Cohort 3b ) Biceps Brachii (BB) 240 mg Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Bicpes Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg ACE-083 (Part 2, Open-label) Tibialis Anterior (TA) 240 mg ACE-083 (Part 2, Open-label) Biceps Brachii (BB) 240 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/7 (0.00%)      0/6 (0.00%)      0/15 (0.00%)      0/14 (0.00%)      0/15 (0.00%)      0/14 (0.00%)      0/27 (0.00%)      0/26 (0.00%)    
Hide Serious Adverse Events
ACE-083 (Part 1, Cohort 1a ) Tibialis Anterior (TA) 150mg ACE-083 (Part 1, Cohort 2a ) Tibialis Anterior (TA) 200mg ACE-083 (Part 1, Cohort 3a ) Tibialis Anterior (TA) 200mg ACE-083 (Part 1, Cohort 1b ) Biceps Brachii (BB) 150 mg ACE-083 (Part 1, Cohort 2b ) Biceps Brachii (BB) 200 mg ACE-083 (Part 1, Cohort 3b ) Biceps Brachii (BB) 240 mg Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Bicpes Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg ACE-083 (Part 2, Open-label) Tibialis Anterior (TA) 240 mg ACE-083 (Part 2, Open-label) Biceps Brachii (BB) 240 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/7 (0.00%)      0/6 (0.00%)      0/15 (0.00%)      1/14 (7.14%)      1/15 (6.67%)      1/14 (7.14%)      1/27 (3.70%)      0/26 (0.00%)    
Infections and infestations                         
Diverticulitis  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/14 (0.00%)  0 0/27 (0.00%)  0 0/26 (0.00%)  0
Lung abscess  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/14 (0.00%)  0 0/27 (0.00%)  0 0/26 (0.00%)  0
Sepsis  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/27 (0.00%)  0 0/26 (0.00%)  0
Pneumonia  1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/14 (7.14%)  1 0/27 (0.00%)  0 0/26 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                         
Invasive ductal breast carcinoma  2  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/14 (0.00%)  0 1/27 (3.70%)  1 0/26 (0.00%)  0
1
Term from vocabulary, MedDRA 19.1
2
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
ACE-083 (Part 1, Cohort 1a ) Tibialis Anterior (TA) 150mg ACE-083 (Part 1, Cohort 2a ) Tibialis Anterior (TA) 200mg ACE-083 (Part 1, Cohort 3a ) Tibialis Anterior (TA) 200mg ACE-083 (Part 1, Cohort 1b ) Biceps Brachii (BB) 150 mg ACE-083 (Part 1, Cohort 2b ) Biceps Brachii (BB) 200 mg ACE-083 (Part 1, Cohort 3b ) Biceps Brachii (BB) 240 mg Placebo (Part 2, DB-PC) Tibialis Anterior (TA) ACE-083 (Part 2, DB-PC) Tibialis Anterior (TA) 240 mg Placebo (Part 2, DB-PC) Bicpes Brachii (BB) ACE-083 (Part 2, DB-PC) Biceps Brachii (BB) 240 mg ACE-083 (Part 2, Open-label) Tibialis Anterior (TA) 240 mg ACE-083 (Part 2, Open-label) Biceps Brachii (BB) 240 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      6/6 (100.00%)      5/6 (83.33%)      6/6 (100.00%)      7/7 (100.00%)      6/6 (100.00%)      12/15 (80.00%)      14/14 (100.00%)      13/15 (86.67%)      14/14 (100.00%)      22/27 (81.48%)      22/26 (84.62%)    
Cardiac disorders                         
Tachycardia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Ear and labyrinth disorders                         
Vertigo  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Endocrine disorders                         
Thyroid mass  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Eye disorders                         
Cataract  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Macular degeneration  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Ocular hyperemia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Diabetic retinopathy  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Retinal detachment  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Conjunctival haemorrhage  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  1/26 (3.85%) 
Gastrointestinal disorders                         
Nausea  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  2/14 (14.29%)  0/27 (0.00%)  0/26 (0.00%) 
Vomiting  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Abdominal pain upper  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  2/26 (7.69%) 
Dyspepsia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Diarrhea  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  2/14 (14.29%)  0/27 (0.00%)  2/26 (7.69%) 
Abdominal hernia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Gastroesophageal reflux disease  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Odynophagia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Toothache  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Anal stenosis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Large intestine polyp  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
General disorders                         
Injection site pain  1  5/6 (83.33%)  4/6 (66.67%)  3/6 (50.00%)  1/6 (16.67%)  4/7 (57.14%)  3/6 (50.00%)  4/15 (26.67%)  5/14 (35.71%)  6/15 (40.00%)  6/14 (42.86%)  6/27 (22.22%)  7/26 (26.92%) 
Injection site discomfort  1  1/6 (16.67%)  1/6 (16.67%)  3/6 (50.00%)  5/6 (83.33%)  0/7 (0.00%)  2/6 (33.33%)  1/15 (6.67%)  3/14 (21.43%)  4/15 (26.67%)  2/14 (14.29%)  3/27 (11.11%)  3/26 (11.54%) 
Injection site erythema  1  0/6 (0.00%)  2/6 (33.33%)  3/6 (50.00%)  2/6 (33.33%)  1/7 (14.29%)  3/6 (50.00%)  0/15 (0.00%)  6/14 (42.86%)  5/15 (33.33%)  3/14 (21.43%)  1/27 (3.70%)  9/26 (34.62%) 
Injection site swelling  1  0/6 (0.00%)  3/6 (50.00%)  2/6 (33.33%)  1/6 (16.67%)  2/7 (28.57%)  2/6 (33.33%)  0/15 (0.00%)  2/14 (14.29%)  0/15 (0.00%)  3/14 (21.43%)  1/27 (3.70%)  6/26 (23.08%) 
Injection site bruising  1  1/6 (16.67%)  1/6 (16.67%)  2/6 (33.33%)  4/6 (66.67%)  4/7 (57.14%)  5/6 (83.33%)  2/15 (13.33%)  2/14 (14.29%)  10/15 (66.67%)  9/14 (64.29%)  1/27 (3.70%)  15/26 (57.69%) 
Injection site paraesthesia  1  1/6 (16.67%)  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  1/14 (7.14%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Injection site pruritus  1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/7 (0.00%)  1/6 (16.67%)  0/15 (0.00%)  6/14 (42.86%)  1/15 (6.67%)  2/14 (14.29%)  1/27 (3.70%)  4/26 (15.38%) 
Vessel puncture site bruise  1  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/15 (0.00%)  1/14 (7.14%)  1/15 (6.67%)  5/14 (35.71%)  0/27 (0.00%)  0/26 (0.00%) 
Injection site hemorrhage  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  3/15 (20.00%)  0/14 (0.00%)  0/27 (0.00%)  1/26 (3.85%) 
Injection site warmth  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  1/15 (6.67%)  3/14 (21.43%)  1/15 (6.67%)  1/14 (7.14%)  2/27 (7.41%)  2/26 (7.69%) 
Pain  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Injection site discoloration  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  2/6 (33.33%)  0/15 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Application site rash  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/15 (0.00%)  1/14 (7.14%)  1/15 (6.67%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Influenza like illness  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Injection site induration  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  2/26 (7.69%) 
Injection site papule  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/15 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  1/26 (3.85%) 
Peripheral swelling  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/15 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  2/14 (14.29%)  0/27 (0.00%)  0/26 (0.00%) 
Vessel puncture site erythema  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Fatigue  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  2/14 (14.29%)  0/15 (0.00%)  2/14 (14.29%)  1/27 (3.70%)  0/26 (0.00%) 
Feeling hot  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  1/14 (7.14%)  0/15 (0.00%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Asthenia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Chest discomfort  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Discomfort  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Gait disturbance  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Injection site coldness  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Injection site hematoma  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Injection site hypoesthesia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Injection site rash  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Injection site dysaesthesia  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Mass  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Oedema peripheral  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Immune system disorders                         
Seasonal allergy  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  1/26 (3.85%) 
Infections and infestations                         
Nasopharyngitis  1  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  0/7 (0.00%)  1/6 (16.67%)  1/15 (6.67%)  2/14 (14.29%)  3/15 (20.00%)  2/14 (14.29%)  0/27 (0.00%)  4/26 (15.38%) 
Acne pustular  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Bronchitis  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Chronic sinusitis  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Influenza  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  1/15 (6.67%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Upper respiratory tract infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  1/15 (6.67%)  0/14 (0.00%)  0/15 (0.00%)  2/14 (14.29%)  2/27 (7.41%)  0/26 (0.00%) 
Wound infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Otitis media  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Sinusitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  1/27 (3.70%)  0/26 (0.00%) 
Diverticulitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Gastrointestinal viral  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  2/15 (13.33%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Gastroenteritis viral  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Tooth infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Urinary tract infection  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  1/26 (3.85%) 
Injury, poisoning and procedural complications                         
Fall  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  1/6 (16.67%)  2/15 (13.33%)  1/14 (7.14%)  1/15 (6.67%)  2/14 (14.29%)  2/27 (7.41%)  1/26 (3.85%) 
Contusion  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  2/7 (28.57%)  0/6 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  2/27 (7.41%)  1/26 (3.85%) 
Joint injury  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Limb injury  1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Skin abrasion  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Arthropod bite  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  1/26 (3.85%) 
Laceration  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  1/14 (7.14%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Nerve injury  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Procedural anxiety  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  1/14 (7.14%)  0/27 (0.00%)  0/26 (0.00%) 
Epicondylitis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Scratch  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Tooth fracture  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Concussion  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  1/26 (3.85%) 
Eye contusion  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Ligament sprain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  1/26 (3.85%) 
Muscle strain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Post-traumatic pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Procedural pain  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  1/26 (3.85%) 
Road traffic accident  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Investigations                         
Myoglobin blood increased  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Urine analysis abnormal  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  2/27 (7.41%)  0/26 (0.00%) 
Weight increased  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Blood creatine phosphokinase increased  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Blood pressure increased  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Metabolism and nutrition disorders                         
Gout  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Lactic acidosis  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Vitamin D deficiency  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Vitamin B12 deficiency  1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Musculoskeletal and connective tissue disorders                         
Myalgia  1  2/6 (33.33%)  1/6 (16.67%)  2/6 (33.33%)  2/6 (33.33%)  2/7 (28.57%)  1/6 (16.67%)  1/15 (6.67%)  2/14 (14.29%)  0/15 (0.00%)  4/14 (28.57%)  1/27 (3.70%)  2/26 (7.69%) 
Pain in extremity  1  3/6 (50.00%)  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  2/15 (13.33%)  1/14 (7.14%)  1/15 (6.67%)  2/14 (14.29%)  2/27 (7.41%)  0/26 (0.00%) 
Arthralgia  1  0/6 (0.00%)  2/6 (33.33%)  2/6 (33.33%)  1/6 (16.67%)  1/7 (14.29%)  0/6 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  1/15 (6.67%)  1/14 (7.14%)  1/27 (3.70%)  1/26 (3.85%) 
Muscle Spasms  1  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  2/15 (13.33%)  0/14 (0.00%)  1/15 (6.67%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Joint swelling  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  4/14 (28.57%)  1/15 (6.67%)  0/14 (0.00%)  1/27 (3.70%)  0/26 (0.00%) 
Medial tibial stress syndrome  1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)  0/26 (0.00%) 
Muscle swelling  1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/15 (0.00%)  0/14 (0.00%)  0/27 (0.00%)