Trial Outcomes & Findings for Varenicline vs Placebo for the Treatment of Methamphetamine Dependence (NCT NCT01011829)

Last Updated: 2013-03-14

Results Overview

Urine samples, collected thrice weekly, were tested for metabolites of MA using radioimmunoassay. Each subject had a possible of 24 urine drug screens to provide during the 8 weeks of medication. An aggregate measure of urine drug screen results was calculated - the Treatment Effectiveness Score (TES) - which is the average of the sum of MA-free urine specimens provided during the treatment period by participants in each treatment condition.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

8-weeks

Results posted on

2013-03-14

Participant Flow

Twenty treatment-seeking adults with current methamphetamine (MA) dependence were recruited through advertisements in newspapers, the internet, radio and community outreach from Nov 2009 to Feb 2010.

All potential subjects were consented and then completed study screening measures over a max. of six study visits in order to determine study eligibility. Subjects had to be over 18 years old, MA dependent, and looking for treatment with no Axis I disorder not related to substance abuse and have no contraindications for use of varenicline.

Participant milestones

Participant milestones
Measure	Varenicline Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 8).	Placebo (Sugar Pill) 8 weeks of daily matching oral placebo in tablet form
Overall Study STARTED	10	10
Overall Study COMPLETED	6	1
Overall Study NOT COMPLETED	4	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Varenicline vs Placebo for the Treatment of Methamphetamine Dependence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Varenicline n=10 Participants Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 8).	Placebo (Sugar Pill) n=10 Participants 8 weeks of daily matching oral placebo in tablet form	Total n=20 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	10 Participants n=5 Participants	10 Participants n=7 Participants	20 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	37.1 years STANDARD_DEVIATION 10.4 • n=5 Participants	35.1 years STANDARD_DEVIATION 10.5 • n=7 Participants	36.1 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants

PRIMARY outcome

Timeframe: 8-weeks

Population: Intention to treat

Outcome measures

Outcome measures
Measure	Varenicline n=24 Urine drug screen results Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 8).	Placebo (Sugar Pill) n=24 Urine drug screen results 8 weeks of daily matching oral placebo in tablet form
Change in MA Positive Urine Drug Screens Among Participants Randomly Assigned to Receive Varenicline Versus Placebo.	7.4 total MA-free urine drug screens Standard Deviation 10	2.3 total MA-free urine drug screens Standard Deviation 4.8

SECONDARY outcome

Timeframe: 8-weeks

Population: Intention to treat

Retention was determined by the proportion of participants retained for the entire trial and time until drop-out.

Outcome measures

Outcome measures
Measure	Varenicline n=10 Participants Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 8).	Placebo (Sugar Pill) n=10 Participants 8 weeks of daily matching oral placebo in tablet form
Retention (Completion)	6 participants	1 participants

Adverse Events

Varenicline

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo (Sugar Pill)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Steve Shoptaw PhD

University of California, Los Angeles

Phone: 310 794 0619

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Varenicline n=10 participants at risk Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 8).	Placebo (Sugar Pill) n=10 participants at risk 8 weeks of daily matching oral placebo in tablet form
General disorders Insomnia	30.0% 3/10 • Number of events 4 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Psychiatric disorders Irritability	20.0% 2/10 • Number of events 2 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	30.0% 3/10 • Number of events 3 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Gastrointestinal disorders Nausea	40.0% 4/10 • Number of events 4 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Psychiatric disorders Anxiety	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Psychiatric disorders Dysphoria	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Respiratory, thoracic and mediastinal disorders Infection Upper Respiratory	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
General disorders Vivid Dreams	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Skin and subcutaneous tissue disorders Ecchymosis	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Eye disorders Conjunctivitis	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Gastrointestinal disorders Constipation	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Respiratory, thoracic and mediastinal disorders Coughing	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Psychiatric disorders Depression mental	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
General disorders Dry mouth	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Reproductive system and breast disorders Sexual dysfunction	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
General disorders Fatigue	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
General disorders Flushing	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
General disorders Headache	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
General disorders Sex inhibition	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Psychiatric disorders Panic reaction	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Respiratory, thoracic and mediastinal disorders Postnasal drip	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Immune system disorders Sore throat	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
Psychiatric disorders Mental distress	20.0% 2/10 • Number of events 2 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
General disorders Urinary tract infection	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
General disorders Muscle ache	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
General disorders Paraesthesia	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.
General disorders drug withdrawal syndrome	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.	0.00% 0/10 • Adverse events (AEs) were assessed at each study visit during the 8 weeks of treatment and in the follow up period (4 weeks). Subjects were questioned at each clinic visit about their general health. Any physical or clinical change or illness, whether or not considered study drug related, was recorded on the medical record chart and adverse event case report form. In case of an adverse event thought to reflect drug-related toxicity, evaluation and management ensued.