Trial Outcomes & Findings for A Study of CX157 (TriRima) for the Treatment of Depression (NCT NCT00739908)

NCT ID: NCT00739908

Last Updated: 2012-06-27

Results Overview

The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item checklist designed to measure the overall severity of depressive symptoms in patients with MDD \[Montgomery, 1979\]. Items are rated on a scale of 0-6, with scores ranging from 0 to 60 with 0 being symptom free and 60 being the most severe depression. MADRS was assessed at randomization and Weeks 1, 2, 4 and 6 of the study.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 285 participants
• Primary outcome timeframe: Randomization and study end (Week 6).
• Results posted on: 2012-06-27

Participant Flow

The study was conducted at 14 out-patient medical centers in the United States (US) from 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit).

A total of 587 subjects were screened. Three hundred and two (302) subjects failed to meet study entry criteria, and thus were screen failures. The top three reasons for screen failure were: IDS-SR30 total score cut-off for randomization not met (204 pts); presence of cardiovascular abnormality (18 pts) and Laboratory Abnormalities (14 pts).

Participant milestones

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) CX157 is an investigational compound. The mechanism of action of this compound is Reversible Monoamine oxidase inhibition (MAOI)	Oral Placebo TID Placebo does not have any active medication and is the same as a Sugar Pill.
Overall Study STARTED	142	143
Overall Study COMPLETED	117	118
Overall Study NOT COMPLETED	25	25

Reasons for withdrawal

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) CX157 is an investigational compound. The mechanism of action of this compound is Reversible Monoamine oxidase inhibition (MAOI)	Oral Placebo TID Placebo does not have any active medication and is the same as a Sugar Pill.
Overall Study Adverse Event	5	6
Overall Study Withdrawal by Subject	4	2
Overall Study Lost to Follow-up	14	9
Overall Study Non-Compliance With Study Procedures	2	3
Overall Study Non-Compliance With Study Medication	0	3
Overall Study Lack of Efficacy	0	1
Overall Study Relocation	0	1

Baseline Characteristics

A Study of CX157 (TriRima) for the Treatment of Depression

Baseline characteristics by cohort

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) n=142 Participants CX157 is an investigational compound. The mechanism of action of this compound is Reversible Monoamine oxidase inhibition (MAOI)	Oral Placebo TID n=143 Participants Placebo does not have any active medication and is the same as a Sugar Pill.	Total n=285 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	142 Participants n=5 Participants	138 Participants n=7 Participants	280 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	39.1 years STANDARD_DEVIATION 11.14 • n=5 Participants	38.5 years STANDARD_DEVIATION 11.16 • n=7 Participants	38.8 years STANDARD_DEVIATION 11.14 • n=5 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	81 Participants n=7 Participants	161 Participants n=5 Participants
Sex: Female, Male Male	62 Participants n=5 Participants	62 Participants n=7 Participants	124 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	30 Participants n=5 Participants	32 Participants n=7 Participants	62 Participants n=5 Participants
Race (NIH/OMB) White	102 Participants n=5 Participants	105 Participants n=7 Participants	207 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	142 participants n=5 Participants	143 participants n=7 Participants	285 participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization and study end (Week 6).

Population: mITT population consisted of all patients with at least one post randomzation MADRS score. The primary efficacy variable was the change-from-randomization to each available post-randomization measurement of the MADRS total score, used as the response variable in a mixed model repeated measures (MMRM) analysis.

The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item checklist designed to measure the overall severity of depressive symptoms in patients with MDD [Montgomery, 1979]. Items are rated on a scale of 0-6, with scores ranging from 0 to 60 with 0 being symptom free and 60 being the most severe depression. MADRS was assessed at randomization and Weeks 1, 2, 4 and 6 of the study.

Outcome measures

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) n=139 Participants CX157 is an investigational Reversible Monoamine Oxidase Inhibitor (MAOI)	Oral Placebo TID n=143 Participants No active medication, the same as a Sugar Pill
Change From Randomization in Montgomery and Asberg Depression Rating Scale (MADRS)	-12.5 units on a scale Interval -14.4 to -10.5	-12.3 units on a scale Interval -14.2 to -10.3

SECONDARY outcome

Timeframe: Week 6 or the last available post treatment result (LOCF)

Population: mITT population consisted of all patients with at least one post randomization MADRS score.

MADRS is a 10-item checklist designed to measure the overall severity of depressive symptoms in patients with MDD [Montgomery, 1979]. Items are rated on a scale of 0-6, with scores ranging from 0 to 60 with 0 being symptom free and 60 being the most severe depression. Percentage of participants who achieved a reduction in total MADRS score of at least 50% or more as compared to baseline. MADRS was assessed at randomization and Weeks 1, 2, 4, and 6 of the study. MADRS Responder rate at Week 6 or the last available post treatment result (LOCF) is reported here.

Outcome measures

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) n=139 Participants CX157 is an investigational Reversible Monoamine Oxidase Inhibitor (MAOI)	Oral Placebo TID n=143 Participants No active medication, the same as a Sugar Pill
Montgomery and Asberg Depression Rating Scale (MADRS) Response Rate	31.7 percentage of participants Interval 24.0 to 40.1	34.3 percentage of participants Interval 26.5 to 42.7

SECONDARY outcome

Timeframe: Week 6 or the last available post treatment result (LOCF)

Population: mITT population consisted of all patients with at least one post randomzation MADRS score.

Percentage of participants with total MADRS score of 11 or less. MADRS was assessed at randomization and Weeks 1, 2, 4, and 6 of the study. MADRS Remitter rate at Week 6 or the last available post treatment result (LOCF)is reported here.

Outcome measures

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) n=139 Participants CX157 is an investigational Reversible Monoamine Oxidase Inhibitor (MAOI)	Oral Placebo TID n=143 Participants No active medication, the same as a Sugar Pill
Montgomery and Asberg Depression Rating Scale (MADRS) Remitter Rate	19.4 Percentage of Participants Interval 13.2 to 27.0	23.1 Percentage of Participants Interval 16.4 to 30.9

SECONDARY outcome

Timeframe: Randomization and Week 6 or the last available post treatment result (LOCF)

Population: mITT population consisted of all patients with at least one post randomzation MADRS score.

HADS is a subject-rated questionnaire designed to detect states of anxiety and depression. The HADS consists of 14 questions relating to anxiety or depression, each with a choice of four responses [Zigmond, 1983]. These responses are numerically scored 0-3, with 0 representing the least severe response and 3 representing the most severe response. The highest possible total score is 42. HADS was assessed at randomization and Weeks 1, 2, 4, and 6 of the study. Change from randomization in the HADS total score at Week 6 or the last available post treatment result (LOCF) is reported here.

Outcome measures

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) n=139 Participants CX157 is an investigational Reversible Monoamine Oxidase Inhibitor (MAOI)	Oral Placebo TID n=143 Participants No active medication, the same as a Sugar Pill
The Hospital Anxiety and Depression Scale (HADS)	-8.7 units on a scale Interval -10.1 to -7.2	-8.9 units on a scale Interval -10.3 to -7.5

SECONDARY outcome

Timeframe: Randomization and Week 6 or the last available post treatment result (LOCF)

Population: mITT population consisted of all patients with at least one post randomzation MADRS score.

IDSR-SR 30 measures the severity of depressive symptoms by subjects. This scale has 30 items. The minimum score is 0 and the maximum possible IDS-30 score is 90 (the highest severity). IDS-SR30 was administered at screening, randomization and Weeks 1, 2, 4, and 6. Change from randomization in the IDS-SR30 total score at Week 6 or the last available post treatment result (LOCF) is reported here.

Outcome measures

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) n=139 Participants CX157 is an investigational Reversible Monoamine Oxidase Inhibitor (MAOI)	Oral Placebo TID n=143 Participants No active medication, the same as a Sugar Pill
Inventory of Depressive Symptomatology 30 Item -Self Report (IDS -SR 30 Items)	-22.58 units on a scale Interval -26.34 to -18.82	-23.39 units on a scale Interval -26.99 to -19.79

SECONDARY outcome

Timeframe: Week 6 or the last available post treatment result (LOCF)

Population: mITT population consisted of all patients with at least one post randomzation MADRS score.

The Clinical Global Impression - Improvement of Illness (CGI-I) was rated on a 7-point scale by the investigator to measure subject's total improvement compared to his/her condition at randomization according to the following scale: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. CGI-I was measured at Weeks 1, 2, 4 and 6. Percentage of participants "very much improved" and "much improved" at Week 6 or the last available post treatment result (LOCF) is reported here.

Outcome measures

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) n=139 Participants CX157 is an investigational Reversible Monoamine Oxidase Inhibitor (MAOI)	Oral Placebo TID n=143 Participants No active medication, the same as a Sugar Pill
Clinical Global Impression - Improvement of Illness (CGI-I)	36.7 Percentage of Participants	39.9 Percentage of Participants

SECONDARY outcome

Timeframe: Week 6 or the last available post treatment result (LOCF)

Population: mITT population consisted of all patients with at least one post randomzation MADRS score.

CGI-S measures the study rater's assessment of the severity of depression illness. CGI-S is rated on a scale of 1-7 as follows: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = among the most extremely ill patients. CGI-S was measured at randomization and Weeks 1, 2, 4 and 6. Percentage of subjects reported as normal, not at all ill; borderline mentally ill; and mildly ill is reported here at Week 6 or the last available post treatment result (LOCF).

Outcome measures

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) n=139 Participants CX157 is an investigational Reversible Monoamine Oxidase Inhibitor (MAOI)	Oral Placebo TID n=143 Participants No active medication, the same as a Sugar Pill
Clinical Global Impression - Severity of Illness (CGI-S)	36.7 Percentage of Participants	39.9 Percentage of Participants

Adverse Events

Oral CX157 60 mg TID (Total Daily Dose of 180 mg)

Serious events: 3 serious events

Other events: 39 other events

Deaths: 0 deaths

Oral Placebo TID

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) n=142 participants at risk CX157 is an investigational compound. The mechanism of action of this compound is Reversible Monoamine oxidase inhibition (MAOI)	Oral Placebo TID n=143 participants at risk Placebo does not have any active medication and is the same as a Sugar Pill.
Infections and infestations Urinary Tract Infection (UTI)	0.70% 1/142 • Number of events 1 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)	0.00% 0/143 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)
Injury, poisoning and procedural complications Jaw Fracture	0.00% 0/142 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)	0.70% 1/143 • Number of events 1 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)
Injury, poisoning and procedural complications Skin Laceration	0.00% 0/142 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)	0.70% 1/143 • Number of events 1 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)
Musculoskeletal and connective tissue disorders Intervertebral Disc Protrusion	0.70% 1/142 • Number of events 1 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)	0.00% 0/143 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)
Psychiatric disorders Suicidal Ideation	0.70% 1/142 • Number of events 1 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)	0.00% 0/143 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)
Psychiatric disorders Suicidal Attempt	0.00% 0/142 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)	0.70% 1/143 • Number of events 1 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)

Other adverse events

Measure	Oral CX157 60 mg TID (Total Daily Dose of 180 mg) n=142 participants at risk CX157 is an investigational compound. The mechanism of action of this compound is Reversible Monoamine oxidase inhibition (MAOI)	Oral Placebo TID n=143 participants at risk Placebo does not have any active medication and is the same as a Sugar Pill.
Gastrointestinal disorders Diarrhoea	6.3% 9/142 • Number of events 9 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)	4.2% 6/143 • Number of events 6 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)
Gastrointestinal disorders Dyspepsia	6.3% 9/142 • Number of events 9 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)	4.2% 6/143 • Number of events 6 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)
Infections and infestations Upper Respiratory Tract Infection (URTI)	5.6% 8/142 • Number of events 8 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)	3.5% 5/143 • Number of events 5 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)
Musculoskeletal and connective tissue disorders Arthralgia	4.9% 7/142 • Number of events 7 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)	3.5% 5/143 • Number of events 5 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)
Psychiatric disorders Insomnia	5.6% 8/142 • Number of events 8 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)	3.5% 5/143 • Number of events 5 • 16 September 2008 (date of first subject randomized) to 09 July 2009 (last subject's last visit)

Additional Information

Mahnaz Asgharnejad, Pharm.D.; Daniel Burch, M.D.

CeNeRx BioPharma Inc.

Phone: (919) 655 1435; (919) 674 6041

Email: masgharnejad@cenerx.com; danburch@cenerx.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigators were informed that the first publication or disclosure of study results shall be a complete, joint multicenter publication or disclosure coordinated by CeNeRx. Thereafter, any secondary publications will reference the original publication(s).
• Publication restrictions are in place

Restriction type: OTHER