CURB: Cocaine Use Reduction With Buprenorphine

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT01402492
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH), The Emmes Company, LLC (Industry)
• Enrollment: 302
• Locations: 11
• Arms: 3
• Duration (Months): 18
• Patients Per Site: 27.5
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The aim of this study is to investigate the safety and effectiveness of buprenorphine in the presence of naltrexone for the treatment of cocaine dependence.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence	Drug: Buprenorphine + Naltrexone; Drug: Placebo + Naltrexone	Phase 2/Phase 3

Detailed Description

This project will assess the utility of buprenorphine in the presence of naltrexone as a potential medication useful in reducing cocaine use, commencing a research direction of great importance to both theoretical and practical addiction medicine. Buprenorphine will be provided as sublingual buprenorphine+naloxone tablets (Suboxone®, "BUP"). Naltrexone will be provided as extended-release (XR) naltrexone by injection (Vivitrol®, "XR-NTX").

In this multi-center, double-blind, placebo-controlled trial, participants will randomly assigned to one of three medication conditions: 4mg buprenorphine plus naltrexone (BUP4+XR-NTX), 16mg buprenorphine plus naltrexone (BUP16+XR-NTX), or placebo plus naltrexone (PLB+XR-NTX) for 8 weeks of treatment. Participants will be scheduled for clinic visits three times weekly (for a total of 24 visits across the 8-week treatment period) for observed medication administration, provision of take-home medication, collection of safety, medical, drug use, psychological, and compliance measures. In addition, all participants will be scheduled for once-weekly individual Cognitive Behavioral Therapy (CBT) sessions.

This protocol will explore the effects of these three medication conditions to test buprenorphine as a possible treatment for cocaine dependence. This study will advance the science, provide dosing information, and characterize the effects of the combination of the two medications in this population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 302 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Cocaine Use Reduction With Buprenorphine (CURB)
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BUP4+XR-NTX 4mg buprenorphine plus naltrexone for 8 weeks of treatment	Drug: Buprenorphine + Naltrexone; Following a successful naloxone challenge, induction onto extended-release naltrexone by injection (Vivitrol®), and a final assessment of eligibility, participants will be randomly assigned to one of the three conditions: 4mg buprenorphine plus naltrexone, 16 mg buprenorphine plus naltrexone, or placebo plus naltrexone for 8 weeks of treatment. Random assignment will be on a 1:1:1 ratio to one of three conditions. Randomization will be stratified according to site and opioid use levels.; Other Names: Suboxone buprenorphine/naloxone Vivitrol extended release injectable naltrexone
Experimental: BUP16+XR-NTX 16mg buprenorphine plus naltrexone for 8 weeks of treatment	Drug: Buprenorphine + Naltrexone; Following a successful naloxone challenge, induction onto extended-release naltrexone by injection (Vivitrol®), and a final assessment of eligibility, participants will be randomly assigned to one of the three conditions: 4mg buprenorphine plus naltrexone, 16 mg buprenorphine plus naltrexone, or placebo plus naltrexone for 8 weeks of treatment. Random assignment will be on a 1:1:1 ratio to one of three conditions. Randomization will be stratified according to site and opioid use levels.; Other Names: Suboxone buprenorphine/naloxone Vivitrol extended release injectable naltrexone
Active Comparator: PLB+XR-NTX naltrexone for 8 weeks of treatment	Drug: Placebo + Naltrexone; Following a successful naloxone challenge, induction onto extended-release naltrexone by injection (Vivitrol®), and a final assessment of eligibility, participants will be randomly assigned to one of the three conditions: 4mg buprenorphine plus naltrexone, 16 mg buprenorphine plus naltrexone, or placebo plus naltrexone for 8 weeks of treatment. Random assignment will be on a 1:1:1 ratio to one of three conditions. Randomization will be stratified according to site and opioid use levels.; Other Names: Vivitrol extended release injectable naltrexone

Outcome Measures

Primary Outcome Measures

1. Cocaine Use Days as Measured by Self-report, Corroborated by Thrice-weekly Urine Drug Screens [final 30 days of Treatment Phase, study days 25-54]

   Self-reported days of cocaine use corroborated with urine drug screens (UDS).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 to 65 years of age

• In good general health

• Meet Diagnostic and Statistical Manual (DSM)-IV criteria for cocaine dependence

• Meet DSM-IV criteria for past-year opioid dependence OR past-year opioid abuse OR have past-year opioid use and a history of opioid dependence during the lifetime

• Interested in receiving treatment for cocaine dependence

• Able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study

• Able to satisfy and comply with study procedures and requirements

• If female of childbearing potential, willing to practice and effective method of birth control for the duration of the study

Exclusion Criteria:

• Pregnant or breastfeeding females

• Known allergy or sensitivity to study medications

• Recent or ongoing treatment with medications that, in the judgment of the study medical clinician, could interact adversely with study drugs or interfere with study participation

• Have a current pattern of alcohol, benzodiazepine, or other sedative-hypnotic use, as determined by the study medical clinician, which would preclude safe participation

• Liver function test results greater than 5 times the upper limit of normal or other exclusionary clinical lab test values

• Serious medical condition or acute psychiatric disorder that would make study participation difficult or unsafe

• Pending action or situation that might prevent remaining in the area for the duration of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Integrated Substance Abuse Programs (ISAP)	Los Angeles	California	United States	90025
2	Bay Area Addiction Research and Treatment (BAART)	San Francisco	California	United States	94102
3	Addiction Research and Treatment Services (ARTS)	Denver	Colorado	United States	80206
4	Howard University Hospital	Washington	District of Columbia	United States	20060
5	Atlanta VA Medical Center	Atlanta	Georgia	United States	30345
6	Albert Einstein College of Medicine - Division of Substance Abuse	Bronx	New York	United States	10461
7	Bellevue Hospital Center	New York	New York	United States	10016
8	Maryhaven	Columbus	Ohio	United States	43207
9	CODA, Inc.	Portland	Oregon	United States	97214
10	South Texas Veterans Health Care System	San Antonio	Texas	United States	78229
11	Recovery Centers of King County (RCKC)	Seattle	Washington	United States	98122

Sponsors and Collaborators

• University of California, Los Angeles
• National Institute on Drug Abuse (NIDA)
• The Emmes Company, LLC

Investigators

• Principal Investigator: Walter Ling, M.D., University of California, Los Angeles
• Principal Investigator: Andrew J. Saxon, M.D., VA Puget Sound Health Care System
• Principal Investigator: Larissa J. Mooney, M.D., University of California, Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• National Institute on Drug Abuse Clinical Trials Network Website
• Clinical Trials Network Dissemination Library Website
• UCLA Integrated Substance Abuse Programs Website

Publications

None provided.

• Responsible Party: University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT01402492
• Other Study ID Numbers: NIDA-CTN-0048; U10DA013045
• First Posted: Jul 26, 2011
• Last Update Posted: Oct 29, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by University of California, Los Angeles: Cocaine-Related disorders; Cocaine; Substance-Related disorders; Opioid abuse; Opioid dependence; abuse; addiction; treatment; buprenorphine; naltrexone; Suboxone; Vivitrol
• Additional relevant MeSH terms: Cocaine-Related Disorders; Naltrexone; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Naloxone

Study Results

Participant Flow

Arm/Group Title	BUP4+XR-NTX	BUP16+XR-NTX	PLB+XR-NTX
Arm/Group Description	4mg buprenorphine plus naltrexone for 8 weeks of treatment	16mg buprenorphine plus naltrexone for 8 weeks of treatment	Placebo plus naltrexone for 8 weeks of treatment
Period Title: Overall Study
STARTED	100	100	102
COMPLETED	79	83	86
NOT COMPLETED	21	17	16

Baseline Characteristics

Arm/Group Title	BUP4+XR-NTX	BUP16+XR-NTX	PLB+XR-NTX	Total
Arm/Group Description	4mg buprenorphine plus naltrexone for 8 weeks of treatment	16mg buprenorphine plus naltrexone for 8 weeks of treatment	Placebo plus naltrexone for 8 weeks of treatment	Total of all reporting groups
Overall Participants	100	100	102	302
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	100 100%	100 100%	102 100%	302 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.8 (8.00)	45.8 (10.08)	46.5 (7.68)	46.3 (8.63)
Age, Customized (years) [Number]
18-24	0	3	0	3
25-34	9	14	7	30
35-44	27	19	26	72
45-54	46	45	55	146
55-64	18	19	14	51
Sex: Female, Male (Count of Participants)
Female	20 20%	22 22%	23 22.5%	65 21.5%
Male	80 80%	78 78%	79 77.5%	237 78.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 12%	8 8%	11 10.8%	31 10.3%
Not Hispanic or Latino	88 88%	92 92%	91 89.2%	271 89.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 2%	0 0%	2 2%	4 1.3%
Asian	1 1%	0 0%	0 0%	1 0.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	58 58%	68 68%	65 63.7%	191 63.2%
White	26 26%	25 25%	27 26.5%	78 25.8%
More than one race	5 5%	5 5%	6 5.9%	16 5.3%
Unknown or Not Reported	8 8%	2 2%	2 2%	12 4%
Region of Enrollment (participants) [Number]
United States	100 100%	100 100%	102 100%	302 100%

Outcome Measures

1. Primary Outcome

Title	Cocaine Use Days as Measured by Self-report, Corroborated by Thrice-weekly Urine Drug Screens
Description	Self-reported days of cocaine use corroborated with urine drug screens (UDS).
Time Frame	final 30 days of Treatment Phase, study days 25-54

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BUP4+XR-NTX	BUP16+XR-NTX	PLB+XR-NTX
Arm/Group Description	4mg buprenorphine plus naltrexone for 8 weeks of treatment	16mg buprenorphine plus naltrexone for 8 weeks of treatment	Placebo plus naltrexone for 8 weeks of treatment
Measure Participants	100	100	102
Mean (Standard Deviation) [days of cocaine use]	6.6 (5.25)	7.2 (6.77)	7.7 (6.16)

Adverse Events

Arm/Group Title	BUP4+XR-NTX		BUP16+XR-NTX		PLB+XR-NTX
Arm/Group Description	4mg buprenorphine plus naltrexone for 8 weeks of treatment		16mg buprenorphine plus naltrexone for 8 weeks of treatment		Placebo plus naltrexone for 8 weeks of treatment
All Cause Mortality
	BUP4+XR-NTX		BUP16+XR-NTX		PLB+XR-NTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	BUP4+XR-NTX		BUP16+XR-NTX		PLB+XR-NTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/100 (13%)		8/100 (8%)		12/102 (11.8%)
Gastrointestinal disorders
Pancreatitis	1/100 (1%)		0/100 (0%)		0/102 (0%)
Oesophagitis	0/100 (0%)		0/100 (0%)		1/102 (1%)
Haematemesis	0/100 (0%)		1/100 (1%)		0/102 (0%)
Gastric Ulcer Perforation	0/100 (0%)		0/100 (0%)		1/102 (1%)
Gastric Ulcer	0/100 (0%)		0/100 (0%)		1/102 (1%)
Diverticulum	0/100 (0%)		0/100 (0%)		1/102 (1%)
General disorders
Chest Pain	2/100 (2%)		0/100 (0%)		0/102 (0%)
Non-Cardiac Chest Pain	1/100 (1%)		0/100 (0%)		0/102 (0%)
Cardiac Death	0/100 (0%)		0/100 (0%)		1/102 (1%)
Infections and infestations
Sinusitis	0/100 (0%)		2/100 (2%)		0/102 (0%)
Wound Infection Staphylococcal	1/100 (1%)		0/100 (0%)		0/102 (0%)
Cellulitis	0/100 (0%)		0/100 (0%)		1/102 (1%)
Injury, poisoning and procedural complications
Toxicity to Various Agents	1/100 (1%)		0/100 (0%)		0/102 (0%)
Investigations
International Normalised Ratio Increased	0/100 (0%)		0/100 (0%)		1/102 (1%)
Musculoskeletal and connective tissue disorders
Lumbar Spinal Stenosis	1/100 (1%)		0/100 (0%)		0/102 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous Cell Carcinoma	1/100 (1%)		0/100 (0%)		0/102 (0%)
Metastases to Spine	0/100 (0%)		1/100 (1%)		0/102 (0%)
Psychiatric disorders
Depression	1/100 (1%)		1/100 (1%)		0/102 (0%)
Suicidal Ideation	0/100 (0%)		0/100 (0%)		1/102 (1%)
Suicidal Behavior	0/100 (0%)		0/100 (0%)		1/102 (1%)
Psychotic Disorder	1/100 (1%)		0/100 (0%)		0/102 (0%)
Major Depression	0/100 (0%)		1/100 (1%)		0/102 (0%)
Renal and urinary disorders
Nephrolithiasis	0/100 (0%)		0/100 (0%)		1/102 (1%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	0/100 (0%)		0/100 (0%)		1/102 (1%)
Chronic Obstructive Pulmonary Disease	0/100 (0%)		0/100 (0%)		1/102 (1%)
Asthma	1/100 (1%)		0/100 (0%)		0/102 (0%)
Skin and subcutaneous tissue disorders
Acute Febrile Neutrophilic Dermatosis	0/100 (0%)		0/100 (0%)		1/102 (1%)
Surgical and medical procedures
Drug Detoxification	2/100 (2%)		1/100 (1%)		1/102 (1%)
Dialysis	0/100 (0%)		1/100 (1%)		0/102 (0%)
Other (Not Including Serious) Adverse Events
	BUP4+XR-NTX		BUP16+XR-NTX		PLB+XR-NTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/100 (66%)		64/100 (64%)		61/102 (59.8%)
Blood and lymphatic system disorders
Neutropenia	1/100 (1%)		0/100 (0%)		0/102 (0%)
Monocytosis	1/100 (1%)		0/100 (0%)		0/102 (0%)
Ear and labyrinth disorders
Tinnitus	0/100 (0%)		1/100 (1%)		0/102 (0%)
Ear Pain	1/100 (1%)		0/100 (0%)		0/102 (0%)
Ear Discomfort	0/100 (0%)		1/100 (1%)		0/102 (0%)
Endocrine disorders
Hyperthyrodism	1/100 (1%)		0/100 (0%)		0/102 (0%)
Adrenal Mass	1/100 (1%)		0/100 (0%)		0/102 (0%)
Eye disorders
Lacrimation Increased	1/100 (1%)		0/100 (0%)		0/102 (0%)
Gastrointestinal disorders
Nausea	28/100 (28%)		32/100 (32%)		21/102 (20.6%)
Vomiting	12/100 (12%)		15/100 (15%)		8/102 (7.8%)
Constipation	10/100 (10%)		10/100 (10%)		9/102 (8.8%)
Diarrhea	3/100 (3%)		9/100 (9%)		8/102 (7.8%)
Dry Mouth	0/100 (0%)		3/100 (3%)		2/102 (2%)
Abdominal Pain	0/100 (0%)		3/100 (3%)		1/102 (1%)
Toothache	1/100 (1%)		3/100 (3%)		0/102 (0%)
Abdominal Discomfort	2/100 (2%)		1/100 (1%)		1/102 (1%)
Abdominal Pain Upper	1/100 (1%)		2/100 (2%)		0/102 (0%)
Diverticulum	0/100 (0%)		0/100 (0%)		1/102 (1%)
Dental Caries	0/100 (0%)		0/100 (0%)		1/102 (1%)
Sensitivity of Teeth	0/100 (0%)		0/100 (0%)		1/102 (1%)
Abdominal Distension	1/100 (1%)		0/100 (0%)		0/102 (0%)
Retching	0/100 (0%)		1/100 (1%)		0/102 (0%)
Peptic Ulcer	0/100 (0%)		0/100 (0%)		1/102 (1%)
Pancreatitis	1/100 (1%)		0/100 (0%)		0/102 (0%)
Oesophagitis	0/100 (0%)		0/100 (0%)		1/102 (1%)
Haematemesis	0/100 (0%)		1/100 (1%)		0/102 (0%)
Gastrooesophageal Reflux Disease	0/100 (0%)		0/100 (0%)		1/102 (1%)
Gastrointestinal Ulcer	0/100 (0%)		1/100 (1%)		0/102 (0%)
Gastric Ulcer Perforation	0/100 (0%)		0/100 (0%)		1/102 (1%)
Gastric Ulcer	0/100 (0%)		0/100 (0%)		1/102 (1%)
Faeces Hard	0/100 (0%)		1/100 (1%)		0/102 (0%)
General disorders
Fatigue	9/100 (9%)		6/100 (6%)		4/102 (3.9%)
Drug Withdrawal Syndrome	2/100 (2%)		2/100 (2%)		3/102 (2.9%)
Irritability	3/100 (3%)		0/100 (0%)		0/102 (0%)
Chest Pain	2/100 (2%)		0/100 (0%)		1/102 (1%)
Non-cardiac Chest Pain	2/100 (2%)		0/100 (0%)		0/102 (0%)
Influenza-like Illness	0/100 (0%)		2/100 (2%)		0/102 (0%)
Sluggishness	0/100 (0%)		1/100 (1%)		0/102 (0%)
Asthenia	1/100 (1%)		0/100 (0%)		0/102 (0%)
Hepatobiliary disorders
Cholelithiasis	0/100 (0%)		1/100 (1%)		0/102 (0%)
Immune system disorders
Seasonal Allergy	2/100 (2%)		0/100 (0%)		0/102 (0%)
Hypersensitivity	0/100 (0%)		1/100 (1%)		0/102 (0%)
Infections and infestations
Nasopharyngitis	1/100 (1%)		1/100 (1%)		3/102 (2.9%)
Tooth Abscess	0/100 (0%)		3/100 (3%)		0/102 (0%)
Sinusitis	0/100 (0%)		2/100 (2%)		1/102 (1%)
Upper Respiratory Tract Infection	0/100 (0%)		0/100 (0%)		2/102 (2%)
Tooth Infection	0/100 (0%)		1/100 (1%)		0/102 (0%)
Periorbital Infection	0/100 (0%)		0/100 (0%)		1/102 (1%)
Haemophilus Infection	0/100 (0%)		0/100 (0%)		1/102 (1%)
Cellulitis	0/100 (0%)		0/100 (0%)		1/102 (1%)
Wound Infection Staphylococcal	1/100 (1%)		0/100 (0%)		0/102 (0%)
Injury, poisoning and procedural complications
Laceration	1/100 (1%)		0/100 (0%)		2/102 (2%)
Toxicity to Various Agents	1/100 (1%)		0/100 (0%)		0/102 (0%)
Thermal Burn	0/100 (0%)		0/100 (0%)		1/102 (1%)
Post-traumatic Neck Syndrome	0/100 (0%)		0/100 (0%)		1/102 (1%)
Post-lumbar Puncture Syndrome	1/100 (1%)		0/100 (0%)		0/102 (0%)
Joint Dislocation	1/100 (1%)		0/100 (0%)		0/102 (0%)
Fall	0/100 (0%)		1/100 (1%)		0/102 (0%)
Ankle Fracture	0/100 (0%)		0/100 (0%)		1/102 (1%)
Alcohol Poisoning	0/100 (0%)		1/100 (1%)		0/102 (0%)
Investigations
Weight Increased	1/100 (1%)		0/100 (0%)		0/102 (0%)
Urine Analysis Abnormal	0/100 (0%)		1/100 (1%)		0/102 (0%)
Liver Function Test Abnormal	1/100 (1%)		0/100 (0%)		0/102 (0%)
International Normalized Ratio Increased	0/100 (0%)		0/100 (0%)		1/102 (1%)
Blood Pressure Increased	0/100 (0%)		1/100 (1%)		0/102 (0%)
Metabolism and nutrition disorders
Decreased Appetitie	4/100 (4%)		3/100 (3%)		2/102 (2%)
Dehydration	0/100 (0%)		2/100 (2%)		0/102 (0%)
Hypokalaemia	1/100 (1%)		0/100 (0%)		0/102 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/100 (3%)		2/100 (2%)		3/102 (2.9%)
Back Pain	2/100 (2%)		2/100 (2%)		2/102 (2%)
Myalgia	1/100 (1%)		1/100 (1%)		1/102 (1%)
Muscle Spasms	1/100 (1%)		0/100 (0%)		1/102 (1%)
Pain in Extremity	1/100 (1%)		0/100 (0%)		0/102 (0%)
Musculoskeletal Pain	0/100 (0%)		0/100 (0%)		1/102 (1%)
Musculoskeletal Chest Pain	0/100 (0%)		1/100 (1%)		0/102 (0%)
Lumbar Spinal Stenosis	1/100 (1%)		0/100 (0%)		0/102 (0%)
Limb Discomfort	1/100 (1%)		0/100 (0%)		0/102 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine Leiomyoma	1/100 (1%)		0/100 (0%)		0/102 (0%)
Squamous Cell Carcinoma	1/100 (1%)		0/100 (0%)		0/102 (0%)
Metastases to Spine	0/100 (0%)		1/100 (1%)		0/102 (0%)
Lung Neoplasm	0/100 (0%)		1/100 (1%)		0/102 (0%)
Nervous system disorders
Dizziness	10/100 (10%)		9/100 (9%)		4/102 (3.9%)
Headache	9/100 (9%)		6/100 (6%)		5/102 (4.9%)
Somnolence	3/100 (3%)		4/100 (4%)		4/102 (3.9%)
Tremor	1/100 (1%)		1/100 (1%)		1/102 (1%)
Sedation	0/100 (0%)		2/100 (2%)		1/102 (1%)
Loss of Consciousness	0/100 (0%)		2/100 (2%)		0/102 (0%)
Dysgeusia	1/100 (1%)		1/100 (1%)		0/102 (0%)
Sciatica	1/100 (1%)		1/100 (1%)		0/102 (0%)
Paraesthesia	1/100 (1%)		0/100 (0%)		0/102 (0%)
Lethargy	1/100 (1%)		0/100 (0%)		0/102 (0%)
Hypoaesthesia	1/100 (1%)		0/100 (0%)		0/102 (0%)
Depressed Level of Consciousness	0/100 (0%)		1/100 (1%)		0/102 (0%)
Tension Headache	1/100 (1%)		0/100 (0%)		0/102 (0%)
Aura	0/100 (0%)		0/100 (0%)		1/102 (1%)
Parosmia	0/100 (0%)		1/100 (1%)		0/102 (0%)
Psychiatric disorders
Insomnia	4/100 (4%)		5/100 (5%)		2/102 (2%)
Depression	3/100 (3%)		2/100 (2%)		2/102 (2%)
Anxiety	1/100 (1%)		5/100 (5%)		0/102 (0%)
Libido Decreased	2/100 (2%)		0/100 (0%)		3/102 (2.9%)
Suicidal Ideation	0/100 (0%)		3/100 (3%)		2/102 (2%)
Euphoric Mood	1/100 (1%)		1/100 (1%)		0/102 (0%)
Depressed Mood	1/100 (1%)		0/100 (0%)		1/102 (1%)
Sleep Disorder	1/100 (1%)		0/100 (0%)		1/102 (1%)
Restlessness	1/100 (1%)		1/100 (1%)		0/102 (0%)
Intentional Self-injury	0/100 (0%)		1/100 (1%)		0/102 (0%)
Drug Dependence	0/100 (0%)		0/100 (0%)		1/102 (1%)
Disorentation	0/100 (0%)		1/100 (1%)		0/102 (0%)
Suicidal Behavior	0/100 (0%)		0/100 (0%)		1/102 (1%)
Substance-induced Mood Disorder	0/100 (0%)		1/100 (1%)		0/102 (0%)
Psychotic Disorder	1/100 (1%)		0/100 (0%)		0/102 (0%)
Panic Attack	1/100 (1%)		0/100 (0%)		0/102 (0%)
Nervousness	0/100 (0%)		1/100 (1%)		0/102 (0%)
Mental Status Changes	0/100 (0%)		0/100 (0%)		1/102 (1%)
Major Depression	0/100 (0%)		1/100 (1%)		0/102 (0%)
Renal and urinary disorders
Urinary Retention	0/100 (0%)		1/100 (1%)		0/102 (0%)
Nephrolithiasis	0/100 (0%)		0/100 (0%)		1/102 (1%)
Dysuria	0/100 (0%)		1/100 (1%)		0/102 (0%)
Respiratory, thoracic and mediastinal disorders
Astma	2/100 (2%)		2/100 (2%)		0/102 (0%)
Nasal Congestion	1/100 (1%)		1/100 (1%)		1/102 (1%)
Dyspnoea	1/100 (1%)		0/100 (0%)		1/102 (1%)
Cough	2/100 (2%)		0/100 (0%)		0/102 (0%)
Rhinorrhoea	1/100 (1%)		0/100 (0%)		0/102 (0%)
Pulmonary Embolism	0/100 (0%)		0/100 (0%)		1/102 (1%)
Pulmonary Congestion	1/100 (1%)		0/100 (0%)		0/102 (0%)
Oropharyngeal Pain	0/100 (0%)		0/100 (0%)		1/102 (1%)
Chronic Obstructive Pulmonary Disease	0/100 (0%)		0/100 (0%)		1/102 (1%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	3/100 (3%)		5/100 (5%)		1/102 (1%)
Pruritus	0/100 (0%)		3/100 (3%)		0/102 (0%)
Cold Sweats	1/100 (1%)		0/100 (0%)		1/102 (1%)
Night Sweats	0/100 (0%)		0/100 (0%)		1/102 (1%)
Acute Febrile Neutrophilic Dermatosis	0/100 (0%)		0/100 (0%)		1/102 (1%)
Surgical and medical procedures
Drug Detoxification	2/100 (2%)		1/100 (1%)		1/102 (1%)
Tooth Extraction	0/100 (0%)		1/100 (1%)		0/102 (0%)
Dialysis	0/100 (0%)		1/100 (1%)		0/102 (0%)
Vascular disorders
Hot Flush	1/100 (1%)		1/100 (1%)		0/102 (0%)
Hypertensive Crisis	0/100 (0%)		0/100 (0%)		1/102 (1%)
Hypertension	0/100 (0%)		0/100 (0%)		1/102 (1%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor can review results communications prior to public release and can embargo communications regarding trial results. The sponsor can require changes to the communication and can extend the embargo.