Trial Outcomes & Findings for ALK21-014: Efficacy and Safety of Medisorb® Naltrexone (VIVITROL®) After Enforced Abstinence (NCT NCT00501631)

Last Updated: 2011-09-22

Results Overview

Cumulative percentage (%) of subjects reporting heavy drinking by category reflecting the various cut-offs for percentage of days that were heavy drinking days. A "heavy drinking day" was defined as 4 or more alcohol drinks in 1 day for women, and 5 or more alcohol drinks in 1 day for men. The Timeline Follow-Back (TLFB) method (Sobell \& Sobell: Humana Press, 1992) was utilized to collect subjects' daily drinking information (ie, the number of drinks consumed per day per subject which was retrospectively recalled and recorded in a diary).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

300 participants

Primary outcome timeframe

up to 12 weeks

Results posted on

2011-09-22

Participant Flow

Participant milestones

Participant milestones
Measure	VIVITROL 380 mg Arm includes all subjects who received at least 1 injection of VIVITROL. After successfully completing screening subjects were administered VIVITROL 380 mg by intramuscular (IM) injection every 4 weeks for a total of 3 injections. Randomization was 1:1 (VIVITROL:placebo) and stratified by site.	Placebo for VIVITROL 380 mg All subjects who received at least 1 injection of Placebo for VIVITROL. Arm includes all subjects who received at least 1 injection of placebo. After successfully completing screening subjects were administered placebo by intramuscular (IM) injection every 4 weeks for a total of 3 injections. Randomization was 1:1 (VIVITROL:placebo) and stratified by site.
Part A (Double-blind Period) STARTED	152	148
Part A (Double-blind Period) COMPLETED	90	99
Part A (Double-blind Period) NOT COMPLETED	62	49
Part B (Open-label Period) STARTED	90	99
Part B (Open-label Period) COMPLETED	37	48
Part B (Open-label Period) NOT COMPLETED	53	51

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ALK21-014: Efficacy and Safety of Medisorb® Naltrexone (VIVITROL®) After Enforced Abstinence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VIVITROL 380 mg n=152 Participants Arm includes all subjects who received at least 1 injection of VIVITROL. After successfully completing screening subjects were administered VIVITROL 380 mg by intramuscular (IM) injection every 4 weeks for a total of 3 injections. Randomization was 1:1 (VIVITROL:placebo) and stratified by site.	Placebo for VIVITROL 380 mg n=148 Participants All subjects who received at least 1 injection of Placebo for VIVITROL. Arm includes all subjects who received at least 1 injection of placebo. After successfully completing screening subjects were administered placebo by intramuscular (IM) injection every 4 weeks for a total of 3 injections. Randomization was 1:1 (VIVITROL:placebo) and stratified by site.	Total n=300 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	152 Participants n=99 Participants	148 Participants n=107 Participants	300 Participants n=206 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age Continuous	45.5 years STANDARD_DEVIATION 8.5 • n=99 Participants	46.1 years STANDARD_DEVIATION 8.3 • n=107 Participants	45.8 years STANDARD_DEVIATION 8.4 • n=206 Participants
Sex: Female, Male Female	33 Participants n=99 Participants	27 Participants n=107 Participants	60 Participants n=206 Participants
Sex: Female, Male Male	119 Participants n=99 Participants	121 Participants n=107 Participants	240 Participants n=206 Participants
Region of Enrollment Germany	142 participants n=99 Participants	138 participants n=107 Participants	280 participants n=206 Participants
Region of Enrollment Austria	10 participants n=99 Participants	10 participants n=107 Participants	20 participants n=206 Participants

PRIMARY outcome

Timeframe: up to 12 weeks

Population: The primary endpoint is based on percentage rate of heavy drinking days during the double-blind treatment period as per protocol.

Outcome measures

Outcome measures
Measure	Vivitrol n=152 Participants	Placebo n=148 Participants
Cumulative Percentage of Participants by Heavy Drinking Rate 0% Heavy Drinking Days	40.8 percentage of participants	47.3 percentage of participants
Cumulative Percentage of Participants by Heavy Drinking Rate <= 10% Heavy Drinking Days	59.2 percentage of participants	59.5 percentage of participants
Cumulative Percentage of Participants by Heavy Drinking Rate <= 20% Heavy Drinking Days	65.8 percentage of participants	72.3 percentage of participants
Cumulative Percentage of Participants by Heavy Drinking Rate <= 30% Heavy Drinking Days	74.3 percentage of participants	79.1 percentage of participants
Cumulative Percentage of Participants by Heavy Drinking Rate <= 40% Heavy Drinking Days	80.9 percentage of participants	83.1 percentage of participants
Cumulative Percentage of Participants by Heavy Drinking Rate <= 50% Heavy Drinking Days	83.6 percentage of participants	85.1 percentage of participants
Cumulative Percentage of Participants by Heavy Drinking Rate <= 60% Heavy Drinking Days	84.9 percentage of participants	87.2 percentage of participants
Cumulative Percentage of Participants by Heavy Drinking Rate <= 70% Heavy Drinking Days	90.1 percentage of participants	89.9 percentage of participants
Cumulative Percentage of Participants by Heavy Drinking Rate <= 80% Heavy Drinking Days	93.4 percentage of participants	94.6 percentage of participants
Cumulative Percentage of Participants by Heavy Drinking Rate <= 90% Heavy Drinking Days	97.4 percentage of participants	98.6 percentage of participants
Cumulative Percentage of Participants by Heavy Drinking Rate <= 100% Heavy Drinking Days	100.0 percentage of participants	100.0 percentage of participants

SECONDARY outcome

Timeframe: up to 1 year

Number of subjects reporting at least 1 treatment-emergent adverse event (TEAE) while on study.

Outcome measures

Outcome data not reported

Adverse Events

VIVITROL 380 mg (Double-blind Period)

Serious events: 29 serious events

Other events: 135 other events

Deaths: 0 deaths

Placebo for VIVITROL 380 mg (Double-blind Period)

Serious events: 27 serious events

Other events: 133 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bernard L. Silverman, MD

Alkermes, Inc.

Phone: 1-781-609-6000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No individual Investigator may publish results without written agreement from Alkermes. Should an Investigator wish to publish or present the data at a meeting, a copy of the manuscript or abstract must be provided to the Sponsor at least 30 days prior to the submission for review and approval. Any revisions will be negotiated in good faith by the Investigator and Sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	VIVITROL 380 mg (Double-blind Period) n=152 participants at risk	Placebo for VIVITROL 380 mg (Double-blind Period) n=148 participants at risk
Psychiatric disorders Alcoholism	10.5% 16/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	13.5% 20/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Suicidal ideation	1.3% 2/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Depression	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Suicide attempt	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Adjustment disorder	0.00% 0/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Bereavement reaction	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Bipolar disorder	0.00% 0/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Emotional distress	0.00% 0/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Psychosomatic disease	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Somnolence	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Blood and lymphatic system disorders Eosinophilia	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
General disorders Inflammation	0.00% 0/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
General disorders Injection site abscess	0.00% 0/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Infections and infestations Appendicitis	0.00% 0/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Infections and infestations Erysipelas	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Injury, poisoning and procedural complications Ankle fracture	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Injury, poisoning and procedural complications Lower limb fracture	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Reproductive system and breast disorders Endometrial hyperplasia	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Reproductive system and breast disorders Gynaecomastia	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Musculoskeletal and connective tissue disorders Tibia fracture	0.00% 0/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Nervous system disorders Alcoholic seizure	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Respiratory, thoracic and mediastinal disorders Asthma	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Surgical and medical procedures Alcohol detoxification	0.66% 1/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.00% 0/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.

Measure	VIVITROL 380 mg (Double-blind Period) n=152 participants at risk	Placebo for VIVITROL 380 mg (Double-blind Period) n=148 participants at risk
General disorders Injection site pain	35.5% 54/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	39.9% 59/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
General disorders Fatigue	9.9% 15/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	3.4% 5/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
General disorders Injection site induration	4.6% 7/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	2.0% 3/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
General disorders Influenza like illness	3.3% 5/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	2.0% 3/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Alcoholism	16.4% 25/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	27.0% 40/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Sleep disorder	5.3% 8/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	6.8% 10/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Depression	5.9% 9/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	4.7% 7/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Psychiatric disorders Depressed mood	4.6% 7/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	2.0% 3/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Nervous system disorders Headache	16.4% 25/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	16.9% 25/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Nervous system disorders Dizziness	7.2% 11/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	2.7% 4/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Infections and infestations Nasopharyngitis	11.8% 18/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	13.5% 20/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Gastrointestinal disorders Nausea	13.2% 20/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	3.4% 5/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Gastrointestinal disorders Diarrhoea	5.9% 9/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	3.4% 5/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Gastrointestinal disorders Toothache	3.3% 5/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	2.7% 4/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Gastrointestinal disorders Vomiting	3.3% 5/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	0.68% 1/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Musculoskeletal and connective tissue disorders Back pain	6.6% 10/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	4.7% 7/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Musculoskeletal and connective tissue disorders Pain in extremity	3.3% 5/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	6.8% 10/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Musculoskeletal and connective tissue disorders Arthralgia	4.6% 7/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	4.1% 6/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Skin and subcutaneous tissue disorders Rash	0.00% 0/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	4.1% 6/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.
Vascular disorders Hypertension	1.3% 2/152 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.	4.1% 6/148 • AE collection began after a subject signed the informed consent form and continued until 30 days after the last dose of study drug was administered. All volunteered, elicited, and observed AEs were recorded on the AE CRFs.