A study to assess the safety and effect of TC-5214 in patients with major depressive disorder.

Study identifier:D4131C00001

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Phase IIb, Randomized, Double-Blind, Placebo-Controlled, Active Controlled, Parallel Group, Multicenter Study to Assess the Safety and Efficacy of 2 Fixed Dose Groups of TC-5214 (S-mecamylamine) as Monotherapy Treatment in Patients with Major Depressive Disorder Who Exhibit an Inadequate Response to Antidepressant Therapy

Medical condition

Major depressive disorder

Phase

Phase 2

Healthy volunteers

Study drug

TC-5214, Duloxetine, Placebo

Sex

All

Actual Enrollment

145

Study type

Interventional

Age

18 Years - 65 Years

Date

Study Start Date: 01 Feb 2011

Primary Completion Date: 01 Aug 2012

Study Completion Date: 01 Aug 2012

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2012 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Beverly Hills, CA, United States

Location

Research Site

Chino, CA, United States

Location

Research Site

Garden Grove, CA, United States

Location

Research Site

San Diego, CA, United States

Location

Research Site

Torrance, CA, United States

Location

Research Site

Bradenton, FL, United States

Location

Research Site

Coral Springs, FL, United States

Location

Research Site

Jacksonville, FL, United States

Arms	Assigned Interventions
Experimental: 1 TC-5214, 1 mg BID	Drug: TC-5214 Tablet, oral, twice daily for 8 weeks
Experimental: 2 TC-5214, 4 mg BID	Drug: TC-5214 Tablet, oral, twice daily for 8 weeks
Active Comparator: 3 Duloxetine 60 mg Q Day	Drug: Duloxetine Capsule, oral, once daily
Placebo Comparator: 4 Placebo	Drug: Placebo Tablet, oral, twice daily for 8 weeks

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This multicenter study was conducted in Europe, Asia, and North America between 4 February 2011 and 26 April 2012.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
21-day screening/washout and 8-week prospective open-label SSRI(selective serotonin reuptake inhibitors)/SNRI(selective serotonin and norepinephrine reuptake inhibitors) periods to identify population of inadequate responders(<50% reduction in Hamilton Rating Scale for Depression total score of ≥16 and a Clinical Global Impression-Severity ≥4).

Reporting Groups

	Description
1 mg BID TC-5214
4 mg BID TC-5214
60 mg QD Duloxetine
Placebo

Participant Flow: Overall Study

	1 mg BID TC-5214	4 mg BID TC-5214	60 mg QD Duloxetine	Placebo
STARTED	37	36	37	35
COMPLETED	17	9	18	18
NOT COMPLETED	20	27	19	17
Withdrawal by Subject	2	4	1	0
Adverse Event	2	1	2	3
Severe Non-Compliance to Protocol	1	3	1	3
Condition under Investigation Worsened	0	0	0	1
Lack of Efficacy	2	2	0	2
Study-Specific Withdrawal Criteria	1	1	0	0
Lost to Follow-up	1	1	1	0
Other or Study Termination	11	15	14	8

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
1 mg BID TC-5214
4 mg BID TC-5214
60 mg QD Duloxetine
Placebo

Baseline Measures

	1 mg BID TC-5214	4 mg BID TC-5214	60 mg QD Duloxetine	Placebo	Total
Number of Participants [units: Participants]	37	36	37	35	145
Age Continuous [units: years] Mean ± Standard Deviation	44.5 ± 13.03	40.3 ± 12.50	41.8 ± 12.70	40.1 ± 10.49	41.7 ± 12.24
Gender, Male/Female [units: participants]
Female	24	26	22	19	91
Male	13	10	15	16	54
Race/Ethnicity, Customized [units: participants]
White	23	20	23	20	86
Black or African American	1	4	4	5	14
Asian	12	10	9	9	40
Native Hawaiian or other Pacific Islander	0	0	0	0	0
American Indian or Alaska Native	0	0	0	0	0
Other	1	2	1	1	5
Hamilton Rating Scale for Depression-17 items (HAMD-17) total score at randomization ^[1] [units: Scores on a scale] Mean ± Standard Deviation	20.914 ± 3.425	21.371 ± 3.606	21.857 ± 3.499	21.344 ± 4.100	21.372 ± 3.632
Montgomery-Asberg Depression Rating Scale (MADRS) total score at randomization ^[2] [units: Scores on a scale] Mean ± Standard Deviation	27.228 ± 5.202	26.857 ± 5.542	28.600 ± 6.796	27.625 ± 5.320	27.577 ± 5.734

Outcome Measures

1. Primary Outcome Measure: Change in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score from Randomization to End of Treatment [ Time Frame: Randomization (Week 8) to end of treatment (Week 16) ]

Measure Type	Primary
Measure Name	Change in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score from Randomization to End of Treatment
Measure Description	A 10-item scale for the evaluation of depressive symptoms. Each Montgomery Asberg Depression Rating Scale (MADRS) item is rated on a 0 to 6 scale. The MADRS total score is calculated as the sum of the 10 individual item scores; the total score can range from 0 to 60. Higher MADRS scores indicate higher levels of depressive symptoms.
Time Frame	Randomization (Week 8) to end of treatment (Week 16)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Modified intent-to-treat analysis set including all randomized patients who received at least 1 dose of investigational product (TC-5214, duloxetine or placebo) and who had a randomization and at least 1 post-randomization MADRS total score.

Reporting Groups

	Description
1 mg BID TC-5214
4 mg BID TC-5214
60 mg QD Duloxetine
Placebo

Measured Values

	1 mg BID TC-5214	4 mg BID TC-5214	60 mg QD Duloxetine	Placebo
Number of Participants Analyzed [units:participants]	35	35	35	32
Change in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score from Randomization to End of Treatment [units: units on a scale] Least Squares Mean (Standard Error)	-9.1 (2.15)	-11.2 (2.56)	-11.4 (2.14)	-7.6 (2.19)

Statistical Analysis 1 for Change in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score from Randomization to End of Treatment

Groups^[1]	1 mg BID TC-5214, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [MMRM]
P-Value^[4]	0.617
Other^[5]	-1.5
Standard Error of the mean	± 2.95
95% Confidence Interval	( -7.35 to 4.39 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Mixed model repeated measures (MMRM) includes treatment, pooled center, visit, treatment by visit interaction, region, responsiveness, and region by responsiveness as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit treatment by visit interaction, region, responsiveness, and region by responsiveness are fixed effects in the model; pooled center is a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score from Randomization to End of Treatment

Groups^[1]	4 mg BID TC-5214, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [MMRM]
P-Value^[4]	0.277
Other^[5]	-3.6
Standard Error of the mean	± 3.26
95% Confidence Interval	( -10.06 to 2.91 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Mixed model repeated measures (MMRM) includes treatment, pooled center, visit, treatment by visit interaction, region, responsiveness, and region by responsiveness as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit, treatment by visit interaction, region, responsiveness, and region by responsiveness are fixed effects in the model; pooled center is a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Change in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score from Randomization to End of Treatment

Groups^[1]	60 mg QD Duloxetine, Placebo
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Other [MMRM]
P-Value^[4]	0.194
Other^[5]	-3.9
Standard Error of the mean	± 2.95
95% Confidence Interval	( -9.72 to 2.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Mixed model repeated measures (MMRM) includes treatment, pooled center, visit, treatment by visit interaction, region, responsiveness, and region by responsiveness as explanatory variables and the randomization MADRS total score as a covariate. Treatment, visit, treatment by visit interaction, region, responsiveness, and region by responsiveness are fixed effects in the model; pooled center is a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
1 mg BID TC-5214	No text entered.
4 mg BID TC-5214	No text entered.
60 mg QD Duloxetine	No text entered.
Placebo	No text entered.

Serious Adverse Events

1 mg BID TC-5214

4 mg BID TC-5214

60 mg QD Duloxetine

Placebo

Total, serious adverse events

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

Gastrointestinal disorders

Abdominal Pain¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

Infections and infestations

Subcutaneous Abscess¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 15.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	2%

Reporting Groups

	Description
1 mg BID TC-5214	No text entered.
4 mg BID TC-5214	No text entered.
60 mg QD Duloxetine	No text entered.
Placebo	No text entered.

Other Adverse Events

1 mg BID TC-5214

4 mg BID TC-5214

60 mg QD Duloxetine

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

22/37 (59.46%)

27/35 (77.14%)

21/37 (56.76%)

24/35 (68.57%)

Blood and lymphatic system disorders

Anaemia Megaloblastic¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Blood and lymphatic system disorders

Eosinophilia¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

Ear and labyrinth disorders

Tinnitus¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

Eye disorders

Vision Blurred¹,^†

# participants affected / at risk

0/37 (0.00%)

2/35 (5.71%)

0/37 (0.00%)

0/35 (0.00%)

# events

Eye disorders

Eye Pain¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Eye disorders

Visual Impairment¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

1/35 (2.86%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

0/37 (0.00%)

9/35 (25.71%)

2/37 (5.41%)

2/35 (5.71%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

4/37 (10.81%)

3/35 (8.57%)

7/37 (18.92%)

2/35 (5.71%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/37 (2.70%)

3/35 (8.57%)

1/37 (2.70%)

3/35 (8.57%)

# events

Gastrointestinal disorders

Abdominal Pain¹,^†

# participants affected / at risk

2/37 (5.41%)

2/35 (5.71%)

0/37 (0.00%)

1/35 (2.86%)

# events

Gastrointestinal disorders

Dry Mouth¹,^†

# participants affected / at risk

0/37 (0.00%)

2/35 (5.71%)

1/37 (2.70%)

0/35 (0.00%)

# events

Gastrointestinal disorders

Abdominal Pain Upper¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

Gastrointestinal disorders

Dental Caries¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

1/35 (2.86%)

# events

Gastrointestinal disorders

Flatulence¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Gastrointestinal disorders

Toothache¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

General disorders

Asthenia¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

General disorders

Drug Withdrawal Syndrome¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

General disorders

Fatigue¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

1/37 (2.70%)

0/35 (0.00%)

# events

General disorders

Feeling Abnormal¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

General disorders

Feeling Cold¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

General disorders

Pyrexia¹,^†

# participants affected / at risk

1/37 (2.70%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

General disorders

Thirst¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Hepatobiliary disorders

Hepatic Function Abnormal¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Immune system disorders

Seasonal Allergy¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

1/37 (2.70%)

1/35 (2.86%)

2/37 (5.41%)

4/35 (11.43%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

3/37 (8.11%)

2/35 (5.71%)

0/37 (0.00%)

3/35 (8.57%)

# events

Infections and infestations

Urinary Tract Infection¹,^†

# participants affected / at risk

0/37 (0.00%)

2/35 (5.71%)

1/37 (2.70%)

1/35 (2.86%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Infections and infestations

Hordeolum¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Infections and infestations

Tooth Infection¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Infections and infestations

Upper Respiratory Tract Infection¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Infections and infestations

Urethritis¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Injury, poisoning and procedural complications

Procedural Dizziness¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

2/37 (5.41%)

0/35 (0.00%)

# events

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Injury, poisoning and procedural complications

Limb Injury¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Injury, poisoning and procedural complications

Blood Pressure Increased¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

2/35 (5.71%)

# events

Injury, poisoning and procedural complications

Heart Rate Increased¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Injury, poisoning and procedural complications

Weight Decreased¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

Injury, poisoning and procedural complications

Weight Increased¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

1/35 (2.86%)

# events

Metabolism and nutrition disorders

Increased Appetite¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

3/35 (8.57%)

# events

Metabolism and nutrition disorders

Decreased Appetite¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

2/35 (5.71%)

# events

Metabolism and nutrition disorders

Dyslipidaemia¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Metabolism and nutrition disorders

Folate Deficiency¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back Pain¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

3/37 (8.11%)

0/35 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain In Extremity¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

2/37 (5.41%)

0/35 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

1/37 (2.70%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Joint Swelling¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscle Spasms¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

1/37 (2.70%)

0/35 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

1/35 (2.86%)

# events

Musculoskeletal and connective tissue disorders

Neck Pain¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain In Jaw¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

6/37 (16.22%)

4/35 (11.43%)

5/37 (13.51%)

6/35 (17.14%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

4/37 (10.81%)

6/35 (17.14%)

3/37 (8.11%)

5/35 (14.29%)

# events

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

2/37 (5.41%)

1/35 (2.86%)

4/37 (10.81%)

0/35 (0.00%)

# events

Nervous system disorders

Dizziness Postural¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

1/37 (2.70%)

3/35 (8.57%)

# events

Nervous system disorders

Balance Disorder¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

2/37 (5.41%)

1/35 (2.86%)

# events

Nervous system disorders

Paraesthesia¹,^†

# participants affected / at risk

2/37 (5.41%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Nervous system disorders

Disturbance In Attention¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Nervous system disorders

Formication¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Nervous system disorders

Head Discomfort¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

Nervous system disorders

Hypoaesthesia¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Nervous system disorders

Memory Impairment¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Nervous system disorders

Stupor¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

Nervous system disorders

Tremor¹,^†

# participants affected / at risk

1/37 (2.70%)

1/35 (2.86%)

1/37 (2.70%)

1/35 (2.86%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

0/37 (0.00%)

3/35 (8.57%)

4/37 (10.81%)

2/35 (5.71%)

# events

Psychiatric disorders

Agitation¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

1/37 (2.70%)

2/35 (5.71%)

# events

Psychiatric disorders

Nightmare¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

2/35 (5.71%)

# events

Psychiatric disorders

Suicidal Ideation¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

2/35 (5.71%)

# events

Psychiatric disorders

Abnormal Dreams¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

1/35 (2.86%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Psychiatric disorders

Bradyphrenia¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Psychiatric disorders

Confusional State¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Psychiatric disorders

Dissociation¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Psychiatric disorders

Hypervigilance¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

Psychiatric disorders

Intentional Self-Injury¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Psychiatric disorders

Libido Decreased¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

Psychiatric disorders

Mood Swings¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

0/37 (0.00%)

1/35 (2.86%)

# events

Psychiatric disorders

Sleep Disorder¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Psychiatric disorders

Tension¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Renal and urinary disorders

Nocturia¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Renal and urinary disorders

Pollakiuria¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

1/35 (2.86%)

# events

Renal and urinary disorders

Urinary Retention¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Reproductive system and breast disorders

Uterine Polyp¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Skin and subcutaneous tissue disorders

Hyperhidrosis¹,^†

# participants affected / at risk

2/37 (5.41%)

1/35 (2.86%)

1/37 (2.70%)

0/35 (0.00%)

# events

Skin and subcutaneous tissue disorders

Night Sweats¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Skin and subcutaneous tissue disorders

Urticaria¹,^†

# participants affected / at risk

0/37 (0.00%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

1/37 (2.70%)

0/35 (0.00%)

0/37 (0.00%)

0/35 (0.00%)

# events

Vascular disorders

Orthostatic Hypotension¹,^†

# participants affected / at risk

1/37 (2.70%)

1/35 (2.86%)

0/37 (0.00%)

0/35 (0.00%)

# events

Vascular disorders

Varicose Vein¹,^†

# participants affected / at risk

0/37 (0.00%)

0/35 (0.00%)

1/37 (2.70%)

0/35 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 15.0
2	Term from vocabulary,

Certain Agreements

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

There IS 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was terminated early and thus only a fraction of the planned number of patients were randomized and many did not complete the study. As a consequence the possibility of interpreting efficacy over an 8 week period is considerably reduced.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=338&filename=CSR-D4131C00001.pdf
Download
CSR-D4131C00001.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

Quintiles Worldwide

clinical.studies.ns@quintiles.com

Investigators

Principal Investigator

Hans A Eriksson

AstraZeneca R&D Södertälje

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=338&filename=CSR-D4131C00001.pdf

CSR-D4131C00001.pdf

Trial Results Summaries