NTX: Naltrexone for Antipsychotic-Induced Weight Gain

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01866098
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 144
• Location: 1
• Arms: 3
• Duration (Months): 71.2
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

This study is designed to look at the effects of naltrexone on weight loss in individuals treated with antipsychotic medications. Naltrexone is an FDA approved medication for the management of alcohol dependence and drug dependence, but has not been fully evaluated for its effect on weight loss in individuals with severe mental illness (i.e. schizophrenia, schizoaffective disorder, bipolar disorder etc.) The purpose of this study is to find out how effective two different doses of oral naltrexone is on reducing body weight when compared to placebo (an inactive substance or "sugar pill").

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder; Bipolar Disorder; Severe Major Depression With Psychotic Features	Drug: Naltrexone; Drug: Placebo	N/A

Detailed Description

Persons with severe mental illness (SMI) die, on average, 25 years earlier than the general population1. Most of this early mortality can be attributed to cardiovascular disease (CVD) and diabetes mellitus (DM), which are directly related to obesity. Obesity is a leading cause of preventable death in the United States, second only to smoking. The physical health of patients has become a major focus of schizophrenia care, as recent decades have seen immense gains in symptom control and community integration. There is an urgent need for the development of interventions that address the obesity crisis in schizophrenia.

Patients treated with antipsychotic medications have been shown to have a preference for diets high in fat and sugar. Patients with schizophrenia typically seek behaviors that increase dopamine mediated reward in the brain such as smoking and substance use, both of which occur more often in this group than the general population. The system might require intact dopamine and opioid function.

Naltrexone is an oral agent that competitively antagonizes all known opioid receptors in the brain. Human studies with naltrexone were completed in individuals with different illnesses, including schizophrenia, and have been shown to be a safe and easy agent to use. It is shown to decrease craving in alcoholics and is approved by the FDA for the treatment of alcohol dependence. Naltrexone is reported to decrease craving for other substances of abuse, like nicotine. Furthermore, it has been shown to prevent secondary weight gain due to cessation of cigarette smoking at low (25mg and 50 mg), but not higher doses. Naltrexone has been tested in human feeding studies, and has been shown to reduce both the quantity of food eaten and the choice of palatable foods.

Subjects will be randomized to either 25, 50 or 0mg of Naltrexone and will take the study medication daily for 52 weeks. Subjects will be seen weekly for the first 4 weeks of the study, thereafter they will be seen on a bi-weekly (every other week) basis to be assessed (i.e. weight, side effect check, paper questionnaires) throughout the remaining 48 weeks of treatment.

The purpose of this study is to determine the efficacy of two doses of naltrexone (25mg & 50mg) versus placebo for weight and health risk reduction in 144 obese individuals with severe mental illness treated with an antipsychotic medication.

Study Design

• Study Type: Interventional
• Actual Enrollment: 144 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Naltrexone for Antipsychotic-Induced Weight Gain
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Apr 7, 2019
• Actual Study Completion Date: Apr 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Naltrexone 50mg Oral Naltrexone 50mg capsule taken once daily for 52 weeks	Drug: Naltrexone; 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.; Other Names: Revia
Placebo Comparator: Placebo Oral placebo capsule taken once daily for 52 weeks	Drug: Placebo
Experimental: Naltrexone 25mg Oral Naltrexone 25mg capsule taken once daily for 52 weeks	Drug: Naltrexone; 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.; Other Names: Revia

Outcome Measures

Primary Outcome Measures

1. Change in Weight From Baseline [Baseline and 52 weeks]

   Weight (kilograms; kg) will be measured at each assessment and change in weight will be determined at study endpoint.

2. Percent of Subjects Who Lost More Than 5% of Body Weight From Baseline [52 weeks]

   Body Mass Index will be calculated at each assessment and change over time will be assessed at endpoint.

Secondary Outcome Measures

1. Changes in Fasting Glucose From Baseline [Baseline and 52 weeks]

   Fasting glucose will be collected over the course of participation and changes will be evaluated at study endpoint.

2. Changes in Glycosylated Hemoglobin (HbA1c) From Baseline [Baseline and 52 weeks]

   Glycosylated hemoglobin (HbA1c) will be collected over the course of participation and changes will be evaluated at study endpoint.

3. Changes in Insulin From Baseline [Baseline and 52 weeks]

   Insulin will be collected over the course of participation and changes will be evaluated at study endpoint.

4. Changes in Total Cholesterol From Baseline [Baseline and 52 weeks]

   Total Cholesterol will be collected over the course of participation and changes will be evaluated at study endpoint.

5. Changes in HDL From Baseline [Baseline and 52 weeks]

   High-density lipoprotein (HDL) will be collected over the course of participation and changes will be evaluated at study endpoint.

6. Changes in LDL From Baseline [Baseline and 52 weeks]

   Low-density lipoprotein (HDL) will be collected over the course of participation and changes will be evaluated at study endpoint.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 to 75

• Meet Diagnostic & Statistical Manual - 4 (DSM-IV) criteria for schizophrenia, schizoaffective disorder, bipolar disorder, major depression, or another psychotic disorder based on Structured Clinical Interview for the DSM-IV (SCID) interview

• Body Mass Index (BMI) of 28 and over

• On a stable dose of antipsychotic medication; i.e. at least one month with no dose change, and three months from an antipsychotic switch

• Deemed to be symptomatically stable by the clinical staff in the last two months

• Over 7% total body weight increase on antipsychotics for subjects within first year of illness

Exclusion Criteria:

• Meet criteria for current opiate abuse or dependence (confirmed by positive urine drug screen for opiates or, if suspected by study doctor via patient history and or suspicion of occult opiate use, a naloxone challenge will be performed.)

• Current history of dementia, mental retardation

• Not capable of giving informed consent for participation in the study

• Women who are pregnant or breast-feeding

• Physical conditions affecting body weight (e.g. Cushing's disease, polycystic ovary syndrome) Diabetes Mellitus (defined as prescribed an anti-diabetic medication for diabetes or a hemoglobin A1c level > 7 confirmed by primary care physician at screening)

• Severe liver dysfunction, (serum aminotransferases greater than three times normal), acute infectious hepatitis, liver failure.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Connecticut Mental Health Center	New Haven	Connecticut	United States	06519

Sponsors and Collaborators

• Yale University
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Cenk Tek, MD, Yale University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 16, 2017

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01866098
• Other Study ID Numbers: 1207010507; 1R01DK093924-01A1
• First Posted: May 31, 2013
• Last Update Posted: Oct 1, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Yale University: antipsychotic; severe mental illness; weight loss
• Additional relevant MeSH terms: Disease; Weight Gain; Schizophrenia; Bipolar Disorder; Psychotic Disorders; Naltrexone

Study Results

Participant Flow

Arm/Group Title	Placebo	Naltrexone 25mg	Naltrexone 50mg
Arm/Group Description	Oral placebo capsule taken once daily for 52 weeks Placebo	Oral Naltrexone 25mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.	Oral Naltrexone 50mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
Period Title: Overall Study
STARTED	51	47	46
COMPLETED	32	20	25
NOT COMPLETED	19	27	21

Baseline Characteristics

Arm/Group Title	Placebo	Naltrexone 25mg	Naltrexone 50mg	Total
Arm/Group Description	Oral placebo capsule taken once daily for 52 weeks Placebo	Oral Naltrexone 25mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.	Oral Naltrexone 50mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.	Total of all reporting groups
Overall Participants	51	47	46	144
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.8 (12.8)	45.0 (11.5)	43.0 (14.2)	43.6 (12.8)
Sex: Female, Male (Count of Participants)
Female	30 58.8%	22 46.8%	25 54.3%	77 53.5%
Male	21 41.2%	25 53.2%	21 45.7%	67 46.5%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	18 35.3%	16 34%	27 58.7%	61 42.4%
African American	24 47.1%	28 59.6%	16 34.8%	68 47.2%
Other	9 17.6%	3 6.4%	3 6.5%	15 10.4%
Region of Enrollment (participants) [Number]
United States	51 100%	47 100%	46 100%	144 100%
Body Mass Index (BMI) (weight in kg/ height m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weight in kg/ height m^2]	39.1 (7.3)	37.1 (5.7)	38.9 (11.4)	38.4 (8.4)

Outcome Measures

1. Primary Outcome

Title	Change in Weight From Baseline
Description	Weight (kilograms; kg) will be measured at each assessment and change in weight will be determined at study endpoint.
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Analysis population consists of participants who were randomized, received at least 1 dose of the trial compound (naltrexone or placebo), and had at least 1 assessment after baseline.

Arm/Group Title	Placebo	Naltrexone 25mg	Naltrexone 50mg
Arm/Group Description	Oral placebo capsule taken once daily for 52 weeks Placebo	Oral Naltrexone 25mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.	Oral Naltrexone 50mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
Measure Participants	51	47	46
Least Squares Mean (Standard Error) [kg]	-0.16 (1.78)	0.69 (2.22)	-0.95 (2.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Naltrexone 25mg, Naltrexone 50mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Mixed Models Analysis
	Comments	Estimated treatment differences between groups analyzed using mixed-model analysis. Model includes the baseline value age; sex; compliance; ethnicity.

2. Primary Outcome

Title	Percent of Subjects Who Lost More Than 5% of Body Weight From Baseline
Description	Body Mass Index will be calculated at each assessment and change over time will be assessed at endpoint.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Analysis population consists of participants who were randomized, received at least 1 dose of the trial compound (naltrexone or placebo), and had at least 1 assessment after baseline.

Arm/Group Title	Placebo	Naltrexone 25mg	Naltrexone 50mg
Arm/Group Description	Oral placebo capsule taken once daily for 52 weeks Placebo	Oral Naltrexone 25mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.	Oral Naltrexone 50mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
Measure Participants	51	47	46
Count of Participants [Participants]	10 19.6%	4 8.5%	9 19.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Naltrexone 25mg, Naltrexone 50mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Changes in Fasting Glucose From Baseline
Description	Fasting glucose will be collected over the course of participation and changes will be evaluated at study endpoint.
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Analysis population consists of participants who were randomized, received at least 1 dose of the trial compound (naltrexone or placebo), and had at least 1 assessment after baseline.

Arm/Group Title	Placebo	Naltrexone 25mg	Naltrexone 50mg
Arm/Group Description	Oral placebo capsule taken once daily for 52 weeks Placebo	Oral Naltrexone 25mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.	Oral Naltrexone 50mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
Measure Participants	51	47	46
Least Squares Mean (Standard Error) [mg/dL]	8.2 (2.6)	4.6 (3.2)	-0.4 (2.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Naltrexone 25mg, Naltrexone 50mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Mixed Models Analysis
	Comments	Estimated treatment differences between groups analyzed using mixed-model analysis. Model includes the baseline value age; sex; compliance; ethnicity.

4. Secondary Outcome

Title	Changes in Glycosylated Hemoglobin (HbA1c) From Baseline
Description	Glycosylated hemoglobin (HbA1c) will be collected over the course of participation and changes will be evaluated at study endpoint.
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Analysis population consists of participants who were randomized, received at least 1 dose of the trial compound (naltrexone or placebo), and had at least 1 assessment after baseline.

Arm/Group Title	Placebo	Naltrexone 25mg	Naltrexone 50mg
Arm/Group Description	Oral placebo capsule taken once daily for 52 weeks Placebo	Oral Naltrexone 25mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.	Oral Naltrexone 50mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
Measure Participants	51	47	46
Least Squares Mean (Standard Error) [mg/dL]	-0.007 (0.11)	-0.061 (0.15)	0.060 (0.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Naltrexone 25mg, Naltrexone 50mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	Mixed Models Analysis
	Comments	Estimated treatment differences between groups analyzed using mixed-model analysis. Model includes the baseline value age; sex; compliance; ethnicity.

5. Secondary Outcome

Title	Changes in Insulin From Baseline
Description	Insulin will be collected over the course of participation and changes will be evaluated at study endpoint.
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Analysis population consists of participants who were randomized, received at least 1 dose of the trial compound (naltrexone or placebo), and had at least 1 assessment after baseline.

Arm/Group Title	Placebo	Naltrexone 25mg	Naltrexone 50mg
Arm/Group Description	Oral placebo capsule taken once daily for 52 weeks Placebo	Oral Naltrexone 25mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.	Oral Naltrexone 50mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
Measure Participants	51	47	46
Least Squares Mean (Standard Error) [mg/dL]	6.45 (4.89)	0.45 (6.23)	2.16 (5.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Naltrexone 25mg, Naltrexone 50mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	Mixed Models Analysis
	Comments	Estimated treatment differences between groups analyzed using mixed-model analysis. Model includes the baseline value age; sex; compliance; ethnicity.

6. Secondary Outcome

Title	Changes in Total Cholesterol From Baseline
Description	Total Cholesterol will be collected over the course of participation and changes will be evaluated at study endpoint.
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Analysis population consists of participants who were randomized, received at least 1 dose of the trial compound (naltrexone or placebo), and had at least 1 assessment after baseline.

Arm/Group Title	Placebo	Naltrexone 25mg	Naltrexone 50mg
Arm/Group Description	Oral placebo capsule taken once daily for 52 weeks Placebo	Oral Naltrexone 25mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.	Oral Naltrexone 50mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
Measure Participants	51	47	46
Least Squares Mean (Standard Error) [mg/dL]	-1.16 (5.12)	1.52 (6.41)	-3.02 (5.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Naltrexone 25mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	Mixed Models Analysis
	Comments	Estimated treatment differences between groups analyzed using mixed-model analysis. Model includes the baseline value age; sex; compliance; ethnicity.

7. Secondary Outcome

Title	Changes in HDL From Baseline
Description	High-density lipoprotein (HDL) will be collected over the course of participation and changes will be evaluated at study endpoint.
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Analysis population consists of participants who were randomized, received at least 1 dose of the trial compound (naltrexone or placebo), and had at least 1 assessment after baseline.

Arm/Group Title	Placebo	Naltrexone 25mg	Naltrexone 50mg
Arm/Group Description	Oral placebo capsule taken once daily for 52 weeks Placebo	Oral Naltrexone 25mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.	Oral Naltrexone 50mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
Measure Participants	51	47	46
Least Squares Mean (Standard Error) [mg/dL]	0.04 (1.73)	0.79 (2.19)	0.36 (1.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Naltrexone 25mg, Naltrexone 50mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Mixed Models Analysis
	Comments	Estimated treatment differences between groups analyzed using mixed-model analysis. Model includes the baseline value age; sex; compliance; ethnicity.

8. Secondary Outcome

Title	Changes in LDL From Baseline
Description	Low-density lipoprotein (HDL) will be collected over the course of participation and changes will be evaluated at study endpoint.
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Analysis population consists of participants who were randomized, received at least 1 dose of the trial compound (naltrexone or placebo), and had at least 1 assessment after baseline.

Arm/Group Title	Placebo	Naltrexone 25mg	Naltrexone 50mg
Arm/Group Description	Oral placebo capsule taken once daily for 52 weeks Placebo	Oral Naltrexone 25mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.	Oral Naltrexone 50mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
Measure Participants	51	47	46
Least Squares Mean (Standard Error) [mg/dL]	-10.87 (4.47)	1.14 (5.46)	-4.40 (4.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Naltrexone 25mg, Naltrexone 50mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	Mixed Models Analysis
	Comments	Estimated treatment differences between groups analyzed using mixed-model analysis. Model includes the baseline value age; sex; compliance; ethnicity.

Adverse Events

Time Frame	Up to 52 weeks.
Arm/Group Title	Placebo		Naltrexone 25mg		Naltrexone 50mg
Arm/Group Description	Oral placebo capsule taken once daily for 52 weeks Placebo		Oral Naltrexone 25mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.		Oral Naltrexone 50mg capsule taken once daily for 52 weeks Naltrexone: 25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
All Cause Mortality
	Placebo		Naltrexone 25mg		Naltrexone 50mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		1/47 (2.1%)		0/46 (0%)
Serious Adverse Events
	Placebo		Naltrexone 25mg		Naltrexone 50mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		1/47 (2.1%)		0/46 (0%)
General disorders
Cocaine Overdose	0/51 (0%)		1/47 (2.1%)		0/46 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Naltrexone 25mg		Naltrexone 50mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/51 (68.6%)		33/47 (70.2%)		35/46 (76.1%)
Gastrointestinal disorders
Reduced salivation	6/51 (11.8%)		1/47 (2.1%)		1/46 (2.2%)
Nausea	21/51 (41.2%)		20/47 (42.6%)		19/46 (41.3%)
Diarrhea	11/51 (21.6%)		6/47 (12.8%)		7/46 (15.2%)
Constipation	11/51 (21.6%)		10/47 (21.3%)		7/46 (15.2%)
Stomach pain	0/51 (0%)		2/47 (4.3%)		7/46 (15.2%)
General disorders
Asthenia/Fatigability	2/51 (3.9%)		2/47 (4.3%)		5/46 (10.9%)
Tension/Inner unrest	1/51 (2%)		3/47 (6.4%)		1/46 (2.2%)
Nervous system disorders
Concentration difficulties	0/51 (0%)		0/47 (0%)		3/46 (6.5%)
Sleepiness/Sedation	3/51 (5.9%)		5/47 (10.6%)		2/46 (4.3%)
Increased sleep	3/51 (5.9%)		5/47 (10.6%)		1/46 (2.2%)
Reduced sleep	7/51 (13.7%)		3/47 (6.4%)		10/46 (21.7%)
Headache	15/51 (29.4%)		11/47 (23.4%)		13/46 (28.3%)
Dizziness	8/51 (15.7%)		8/47 (17%)		15/46 (32.6%)
Psychiatric disorders
Depression	3/51 (5.9%)		2/47 (4.3%)		0/46 (0%)
Diminished sexual desire	1/51 (2%)		2/47 (4.3%)		3/46 (6.5%)
Skin and subcutaneous tissue disorders
Pruritus	4/51 (7.8%)		0/47 (0%)		1/46 (2.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.