Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in Major Depressive Disorder (MDD)

NCT ID: NCT01312922

Last Updated: 2022-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 555 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2012-12-31

Brief Summary

The overall objective of this trial is to demonstrate clinically relevant superior antidepressant efficacy of the fixed dose combination PNB01 (low dose pipamperone and citalopram) over reference antidepressant treatment with citalopram alone, and a low dose of psychoactive pipamperone alone in patients with moderate to severe Major Depressive Disorder.

This study was specifically designed to assess patient related outcome (PRO) parameters using an Interactive Voice Response System (IVRS) via telephone.

Detailed Description

This is an international, double-blind, centrally randomized (stratified), multicenter study in 555 patients suffering from moderate to severe MDD in up to 40 sites in the USA, Germany and Canada. Eligible out-patients will be treated once daily (QD) with a fixed dose of either PNB01 (PIP 15 mg / CIT 20 mg (Week 1) - PIP 15 mg / CIT 40 mg (Week 2-10)), CIT alone (CIT 20 mg (Week 1) - CIT 40 mg (Week 2-10) or PIP 15 mg alone (Week 1-10) in a 1:1:1 ratio in a double-blind fashion for 10 weeks. Study visits will be conducted 1, 2, 3, 4, 6, 8 and 10 weeks after study treatment initiation. Possible withdrawal effects will be assessed 1 week after study treatment withdrawal.

A blood sample for pharmacokinetic analysis will be collected when drawing blood for routine biochemistry. Patients who provided written informed consent to participate to the study will be asked to provide their consent to participate also to the non-mandatory pharmacogenetic study.

Patient related outcomes will be collected electronically (ePRO) at study visits prior to visiting the investigator by using an Interactive Voice Response System (IVRS) via telephone. Patients wishing or choosing to discontinue the study treatment prematurely will be encouraged to continue to provide their scores, safety data and medications taken, up to the scheduled study end, by telephone.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

PNB01

oral, once daily administration

Group Type: EXPERIMENTAL

PNB01 fixed dose combination of pipamperone and citalopram

Intervention Type: DRUG

oral once daily administration

citalopram

oral, once daily administration

Group Type: ACTIVE_COMPARATOR

Citalopram

Intervention Type: DRUG

oral once daily administration

pipamperone

oral, once daily administration

Group Type: SHAM_COMPARATOR

Pipamperone

Intervention Type: DRUG

oral once daily administration

Interventions

PNB01 fixed dose combination of pipamperone and citalopram

oral once daily administration

Intervention Type: DRUG

Citalopram

oral once daily administration

Intervention Type: DRUG

Pipamperone

oral once daily administration

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patient is informed and given ample time and opportunity to think about her/his participation and has given her/his written informed consent.

2. Patient understands the investigational nature of the trial and is willing and able to comply with the trial requirements.

3. Patient is male or female, aged ≥ 18 years.

4. Patient has MDD according to the DSM IV-R criteria with an existence of depressed mood (DSM-IV-R Crit. A1) and loss of interest/anhedonia (DSM-IV-R Crit. A2) as confirmed by the MINI, lasting for at least 4 weeks and no longer than 18 months (78 weeks) for the current episode, and causing significant functional impairment (DSM-IV-R MDD C- criterion).

5. CGI-S rating of at least 4 and a minimum MADRS total score of 26 using IVRS ePRO at Baseline.

Exclusion Criteria

1. Patient is pregnant, nursing, or is a woman of child-bearing potential who is not surgically sterile, 2 years postmenopausal, or who does not consistently use 2 combined effective methods of contraception (including at least 1 barrier method), unless sexually abstinent.

2. Existence of Mood Disorder with psychotic features and/or high suicidality risk, as confirmed by MINI.

3. Concomitant diagnosis of any additional primary Axis I disorder and presence of any of the following co-morbid disorders: (Hypo)manic episode, Panic Disorder (limited symptom attacks allowed), Obsessive Compulsive Disorder, Post-traumatic Stress Disorder, Alcohol dependence, any other Substance abuse and/or dependence, Psychotic Disorder, Eating Disorder, or General Anxiety Disorder, as confirmed by MINI.

4. Concomitant diagnosis of any primary Axis II disorder.

5. Patient is hospitalized.

6. Patient has a clinically relevant renal dysfunction (e.g. GFR <60mL/min).

7. Patient has hepatic dysfunction (total bilirubin >2.0mg/dL or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than 2 times the upper limit of the reference range).

8. Patient has a malignant neoplastic disease, a documented history of epilepsy (juvenile convulsions excepted) or a documented, in the opinion of the investigator, clinically relevant risk of bleeding (eg. severe bleeding disorder, treatment with warfarin, …).

9. Patient with a documented history or concomitant diagnosis or significant risk of cardiac arrhythmia or dysrhythmia, including a QTc interval of ≥500 ms at Baseline.

10. Patient has any other medical or psychiatric condition, which in the opinion of the investigator, can jeopardize or would compromise the patient's ability to participate in this trial or that would interfere with trial assessments.

11. Patient with documented alcohol or drug abuse, or having a positive standard screen for alcohol or drugs (including benzodiazepines and opioids).

12. Patient received, in the past 7 days treatment with any psychoactive drug prior to randomization, including typical and atypical antipsychotics, hypnotics, antidepressants, anxiolytic drugs, anticonvulsive therapy, opioids, monoamine oxidase (MAO) inhibitors, sedative antihistamines, psychostimulants or amphetamines, dopamine D2 receptor antagonists, butyrophenones, metoclopramide, lithium, anticonvulsants, benzodiazepines, or barbiturates. If patient has received such therapy, a washout period of at least 7 days prior to baseline is required before inclusion in this trial (except fluoxetine: 4 weeks, and St John's Wort or MAO inhibitors: within 2 weeks).

13. Concomitant treatment with diuretics, QT prolongation drugs, or dopamine agonists.

14. Resistant depression defined as having failed to respond to either: a/ 2 previous antidepressants at an adequate dose administered for at least 4 weeks during the current episode; b/ augmentation therapy with any atypical antipsychotic drug

15. Electroconvulsive therapy (ECT) or repetitive Transcranial Magnetic Stimulation therapy (rTMS) within the last 6 months; Vagus Nerve Stimulation (VNS) or Deep Brain Stimulation (DBS) ever.

16. Formal psychotherapy or alternative treatment for 1 week prior to or during the study.

17. Patient has participated in another trial of an investigational agent (including medical device) within the last 3 months prior to baseline or is currently participating in another trial of an investigational drug.

18. Known hypersensitivity to any of the study drugs

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaNeuroBoost N.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael E Thase, MD

Role: STUDY_CHAIR

Director, Mood and Anxiety Section; 3535 Market Street, Suite 670; Philadelphia, PA 19104-3309, United States of America

Max Schmauss, MD

Role: STUDY_CHAIR

Bezirkskrankenhaus Augsburg Klinik für Psychiatrie, Psychotherapie und Psychosomatik Dr.-Mack-Straße 1 D-86156 Augsburg, Germany

Philippe Lemmens, PhD

Role: STUDY_DIRECTOR

Pharmaneuroboost N.V. Alkerstraat 30A B-3570 Alken, Belgium

Locations

Site 103

Glendale, California, United States

Site 101

National City, California, United States

Site 113

Riverside, California, United States

Site 106

San Diego, California, United States

Site 116

San Diego, California, United States

Site 112

Fort Myers, Florida, United States

Site 135

Miami, Florida, United States

Site 108

Winter Park, Florida, United States

Site 133

Atlanta, Georgia, United States

Site 128

Smyrna, Georgia, United States

Site 132

Libertyville, Illinois, United States

Site 117

Schaumburg, Illinois, United States

Site 110

Baltimore, Maryland, United States

Site 109

Flowood, Mississippi, United States

Site 115

New York, New York, United States

Site 126

Beachwood, Ohio, United States

Site 127

Cincinnati, Ohio, United States

Site 124

Middleburg Heights, Ohio, United States

Site 105

Allentown, Pennsylvania, United States

Site 123

Media, Pennsylvania, United States

Site 122

Philadelphia, Pennsylvania, United States

Site 119

Austin, Texas, United States

Site 104

Dallas, Texas, United States

Site 102

Wichita Falls, Texas, United States

Site 107

Kirkland, Washington, United States

Site 134

Seattle, Washington, United States

Site 201

Kelowna, British Columbia, Canada

Site 202

Penticton, British Columbia, Canada

Site 205

Chatham, Ontario, Canada

Site 203

Mississauga, Ontario, Canada

Site 204

Mississauga, Ontario, Canada

Countries

United States; Canada

Other Identifiers

2011-001190-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PNB01-C301

Identifier Type: -

Identifier Source: org_study_id