Trial Outcomes & Findings for Fast-Fail Trials in Mood and Anxiety Spectrum Disorders; Kappa Opioid Receptor Phase 2a (NCT NCT02218736)

Last Updated: 2019-01-08

Results Overview

Establish POC (Proof of Concept) for KOR (Kappa Opioid Receptor) antagonism by evaluating the impact of CERC-501 relative to Placebo on reward-related neural circuitry in terms of ventral striatal activation during anticipation of reward during the Monetary Incentive Delay Task. Evaluation by fMRI (Functional magnetic resonance imaging). The BOLD (Blood Oxygen Level-Dependent) score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

163 participants

Primary outcome timeframe

baseline, Week 8

Results posted on

2019-01-08

Participant Flow

69 participants screen failed, 2 were unable to complete baseline per protocol, 3 withdrew consent prior to baseline.

Participant milestones

Participant milestones
Measure	CERC-501 Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks	Placebo Oral daily administration of 10 mg placebo for 8 weeks placebo: oral dosing of 10 mg placebo daily for 8 weeks
Overall Study STARTED	45	44
Overall Study COMPLETED	33	35
Overall Study NOT COMPLETED	12	9

Reasons for withdrawal

Reasons for withdrawal
Measure	CERC-501 Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks	Placebo Oral daily administration of 10 mg placebo for 8 weeks placebo: oral dosing of 10 mg placebo daily for 8 weeks
Overall Study Withdrawal by Subject	10	9
Overall Study Protocol Violation	2	0

Baseline Characteristics

Fast-Fail Trials in Mood and Anxiety Spectrum Disorders; Kappa Opioid Receptor Phase 2a

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CERC-501 n=45 Participants Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks	Placebo n=44 Participants Oral daily administration of 10 mg placebo for 8 weeks placebo: oral dosing of 10 mg placebo daily for 8 weeks	Total n=89 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	45 Participants n=5 Participants	44 Participants n=7 Participants	89 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	40.7 years STANDARD_DEVIATION 13.30 • n=5 Participants	38.2 years STANDARD_DEVIATION 13.02 • n=7 Participants	39.5 years STANDARD_DEVIATION 13.15 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	27 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=5 Participants	38 Participants n=7 Participants	76 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	28 Participants n=7 Participants	59 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	45 Participants n=5 Participants	44 Participants n=7 Participants	89 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, Week 8

Population: The primary and secondary endpoints are analyzed for patients who meet the definition of completers for week 8 of the study.

Outcome measures

Outcome measures
Measure	CERC-501 n=34 Participants Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks	Placebo n=34 Participants Oral daily administration of 10 mg placebo for 8 weeks placebo: oral dosing of 10 mg placebo daily for 8 weeks
Change in Ventral Striatal Activation Occurring in Anticipation of Reward During the Monetary Incentive Delay Task Measured by fMRI	0.718 Z score Interval 0.487 to 0.95	0.331 Z score Interval 0.103 to 0.559

SECONDARY outcome

Timeframe: 8 weeks

Population: The primary and secondary endpoints are analyzed for patients who meet the definition of completers for week 8 of the study.

To determine if CERC-501 is superior to placebo in improving a clinical self-report measure of anhedonia using the Snaith Hamilton Pleasure Scale (SHAPS). A single value was calculated for the average over 8 weeks. The SHAPS is a well-validated 14-item questionnaire used to assess anhedonia. It asks participants to agree or disagree with statements of hedonic response in pleasurable situations. Four responses are possible: Strongly disagree, Disagree, Agree, or Strongly agree. Each item is worded so that higher scores indicate greater pleasure capacity. A total score is derived by summing the responses to each item. Items answered "strongly agree" are coded as "1", while "strongly disagree" are coded a score of "4." Therefore, scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia.

Outcome measures

Outcome measures
Measure	CERC-501 n=34 Participants Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks	Placebo n=34 Participants Oral daily administration of 10 mg placebo for 8 weeks placebo: oral dosing of 10 mg placebo daily for 8 weeks
Clinical Anhedonia Measured by the Snaith-Hamilton Pleasure Scale (SHAPS; Total Score)	30.777 score on a scale Interval 29.547 to 32.007	32.363 score on a scale Interval 31.157 to 33.568

SECONDARY outcome

Timeframe: baseline, Week 8

Population: The primary and secondary endpoints are analyzed for patients who meet the definition of completers for week 8 of the study.

To evaluate the impact of CERC-501 relative to placebo on a behavioral measure of anhedonia using the Probabilistic Reward Task (PRT). The PRT will be carried out at baseline and after 8 weeks of double-blind treatment to assess the effects on a behavioral outcome measure that assessed reward-related function (level of reward learning). The score obtained is a ratio of the number of times participants correctly choose the high reward stimuli versus the low rewarding stimuli

Outcome measures

Outcome measures
Measure	CERC-501 n=34 Participants Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks	Placebo n=34 Participants Oral daily administration of 10 mg placebo for 8 weeks placebo: oral dosing of 10 mg placebo daily for 8 weeks
Change in Behavioral Measure of Anhedonia Using the Probabilistic Reward Task	0.034 Ratio (Response Bias Score) Interval -0.019 to 0.087	0.019 Ratio (Response Bias Score) Interval -0.03 to 0.068

Adverse Events

CERC-501

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Kathy Hijek, Associate Director of Clinical Operations

Duke Clnical Research Institute

Phone: 919-668-8700

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	CERC-501 n=45 participants at risk Oral dosing of 10 mg CERC-501 (formerly known as LY2456302) administered daily for 8 weeks CERC-501: Oral dosing of 10 mg CERC-501 daily for 8 weeks	Placebo n=44 participants at risk Oral daily administration of 10 mg placebo for 8 weeks placebo: oral dosing of 10 mg placebo daily for 8 weeks
Gastrointestinal disorders Diarrhea	28.9% 13/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	18.2% 8/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Nervous system disorders Headache	22.2% 10/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	22.7% 10/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Psychiatric disorders Suicidal Ideation	20.0% 9/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	15.9% 7/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Skin and subcutaneous tissue disorders Puritus	22.2% 10/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	4.5% 2/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Psychiatric disorders Depression	13.3% 6/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	11.4% 5/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Nervous system disorders Dizziness	13.3% 6/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	11.4% 5/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Psychiatric disorders Anxiety	13.3% 6/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	6.8% 3/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Skin and subcutaneous tissue disorders Dry Skin	8.9% 4/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	11.4% 5/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Gastrointestinal disorders Dry Mouth	8.9% 4/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	9.1% 4/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Nervous system disorders Insomnia	8.9% 4/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	9.1% 4/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Gastrointestinal disorders Nausea	6.7% 3/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	11.4% 5/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Renal and urinary disorders Pollakiuria	8.9% 4/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	6.8% 3/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Skin and subcutaneous tissue disorders Rash	13.3% 6/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Gastrointestinal disorders Constipation	8.9% 4/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
General disorders Fatigue	6.7% 3/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	4.5% 2/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Ear and labyrinth disorders Tinnitus	8.9% 4/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Eye disorders Vission Blurred	8.9% 4/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Nervous system disorders Coordination Abnormal	6.7% 3/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Psychiatric disorders Disturbance in Attention	6.7% 3/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Nervous system disorders Dizziness postural	6.7% 3/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Respiratory, thoracic and mediastinal disorders Non-cardiac chest pain	6.7% 3/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Respiratory, thoracic and mediastinal disorders Restlessness	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	6.8% 3/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Musculoskeletal and connective tissue disorders Arthralgia	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	4.5% 2/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Renal and urinary disorders Dysuria	6.7% 3/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
General disorders Hyperhidrosis	4.4% 2/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Psychiatric disorders Hypersomnia	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	4.5% 2/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
General disorders Irritability	4.4% 2/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Reproductive system and breast disorders Libido decreased	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	4.5% 2/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
General disorders Asthenia	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Musculoskeletal and connective tissue disorders Back Pain	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
General disorders Malaise	4.4% 2/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Reproductive system and breast disorders Menstruation irregular	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	4.5% 2/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Cardiac disorders Palpitations	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	4.5% 2/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Nervous system disorders Panic attack	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
General disorders Pyrexia	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	4.5% 2/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Respiratory, thoracic and mediastinal disorders Sinus congestion	4.4% 2/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	4.5% 2/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Reproductive system and breast disorders Amenorrhoea	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Gastrointestinal disorders Anal pruritus	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Eye disorders Blepharitis	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Cardiac disorders Chest discomfort	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Cardiac disorders Chest pain	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Eye disorders Conjunctivitis	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Musculoskeletal and connective tissue disorders Costochondritis	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Psychiatric disorders Depressive symptom	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Eye disorders Eye pruritus	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Injury, poisoning and procedural complications Fall	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Infections and infestations Fungal infection	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Gastrointestinal disorders Gastrointestinal disorder	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Infections and infestations Herpes Zoster	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Psychiatric disorders Initial insomnia	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Psychiatric disorders Intentional self-injury	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Psychiatric disorders Middle insomnia	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Psychiatric disorders Mood altered	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Musculoskeletal and connective tissue disorders Muscle twitching	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Respiratory, thoracic and mediastinal disorders Musculoskeletal chest pain	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Blood and lymphatic system disorders Neutropenia	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
General disorders Night sweats	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Immune system disorders Seasonal allergy	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Nervous system disorders Sedation	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Psychiatric disorders Self-injurious ideation	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Vascular disorders Syncope	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Injury, poisoning and procedural complications Tendon rupture	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Nervous system disorders Tension headache	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Gastrointestinal disorders Toothache	0.00% 0/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	2.3% 1/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Renal and urinary disorders Urinary track infeciton	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.
Infections and infestations Viral infection	2.2% 1/45 • Adverse events were collected from the time of consent through 12 weeks for all subjects.	0.00% 0/44 • Adverse events were collected from the time of consent through 12 weeks for all subjects.