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

NCT01312922 | Completed Phase 3 Results

• 2 other identifiers: PNB01-C3012011-001190-11
• Study Type: interventional
• Target: 555
• Locations: 2 countries
• Sites: 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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Early and Sustained (Antidepressant) Response (ESR) Rate

  Early and Sustained Response (ESR) is defined as a MADRS total score reduction from Baseline of 50% or more and a MADRS total score ≤16 at Week 2, Week 3, Week 4, and Week 6.

  From (end of) Week 2 visit to (end of) Week 6 visit

Secondary Outcomes (2)

• Change From Baseline in Total MADRS Score at Week 6

  From Baseline (Day 1) to (end of) Week 6

• Change From Baseline in Total SDS Score at Week 6

  From Baseline (Day 1) to (end of) Week 6 visit

Study Arms (3)

PNB01

EXPERIMENTAL

oral, once daily administration

Drug: PNB01 fixed dose combination of pipamperone and citalopram

citalopram

ACTIVE COMPARATOR

oral, once daily administration

Drug: Citalopram

pipamperone

SHAM COMPARATOR

oral, once daily administration

Drug: Pipamperone

Interventions

PNB01 fixed dose combination of pipamperone and citalopram DRUG

oral once daily administration

PNB01

Citalopram DRUG

oral once daily administration

citalopram

Pipamperone DRUG

oral once daily administration

pipamperone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is informed and given ample time and opportunity to think about her/his participation and has given her/his written informed consent.
• Patient understands the investigational nature of the trial and is willing and able to comply with the trial requirements.
• Patient is male or female, aged ≥ 18 years.
• 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).
• CGI-S rating of at least 4 and a minimum MADRS total score of 26 using IVRS ePRO at Baseline.

You may not qualify if:

• 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.
• Existence of Mood Disorder with psychotic features and/or high suicidality risk, as confirmed by MINI.
• 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.
• Concomitant diagnosis of any primary Axis II disorder.
• Patient is hospitalized.
• Patient has a clinically relevant renal dysfunction (e.g. GFR \<60mL/min).
• 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).
• 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, …).
• 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.
• 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.
• Patient with documented alcohol or drug abuse, or having a positive standard screen for alcohol or drugs (including benzodiazepines and opioids).
• Concomitant treatment with diuretics, QT prolongation drugs, or dopamine agonists.
• 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
• 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.
• Formal psychotherapy or alternative treatment for 1 week prior to or during the study.

Sponsors & Collaborators

• PharmaNeuroBoost N.V.: lead

Study Sites (31)

Site 103

Glendale, California, United States

Location

Site 101

National City, California, United States

Location

Site 113

Riverside, California, United States

Location

Site 106

San Diego, California, United States

Location

Site 116

San Diego, California, United States

Location

Site 112

Fort Myers, Florida, United States

Location

Site 135

Miami, Florida, United States

Location

Site 108

Winter Park, Florida, United States

Location

Site 133

Atlanta, Georgia, United States

Location

Site 128

Smyrna, Georgia, United States

Location

Site 132

Libertyville, Illinois, United States

Location

Site 117

Schaumburg, Illinois, United States

Location

Site 110

Baltimore, Maryland, United States

Location

Site 109

Flowood, Mississippi, United States

Location

Site 115

New York, New York, United States

Location

Site 126

Beachwood, Ohio, United States

Location

Site 127

Cincinnati, Ohio, United States

Location

Site 124

Middleburg Heights, Ohio, United States

Location

Site 105

Allentown, Pennsylvania, United States

Location

Site 123

Media, Pennsylvania, United States

Location

Site 122

Philadelphia, Pennsylvania, United States

Location

Site 119

Austin, Texas, United States

Location

Site 104

Dallas, Texas, United States

Location

Site 102

Wichita Falls, Texas, United States

Location

Site 107

Kirkland, Washington, United States

Location

Site 134

Seattle, Washington, United States

Location

Site 201

Kelowna, British Columbia, Canada

Location

Site 202

Penticton, British Columbia, Canada

Location

Site 205

Chatham, Ontario, Canada

Location

Site 203

Mississauga, Ontario, Canada

Location

Site 204

Mississauga, Ontario, Canada

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Citalopram; pipamperone

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

To avoid limited risk of concluding efficacy when there is no effect, hierarchical testing was implemented with following order of confirmatory tests: 1) Patient-ESR rates of PNB01vs citalopram 2) If above testing is sig., repeat patient-ESR testing for PNB01vs pipamperone 3) In case in 1 of these 2 tests PNB01 does not have sig. higher ESR rate, trial is considered negative, \& no following sec. confirmatory tests are to be executed. Secondary Outcome Measures were therefore not completed

Results Point of Contact

• Title: Dr. E. Buntinx, MD
• Organization: ANeuroTech

erik.buntinx@aneurotech.com

+32 (0) 473 861 079

Study Officials

• Michael E Thase, MD

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

  STUDY CHAIR

• Max Schmauss, MD

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

  STUDY CHAIR

• Philippe Lemmens, PhD

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2011
• First Posted: March 11, 2011
• Study Start: September 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: December 1, 2012
• Last Updated: April 7, 2022
• Results First Posted: April 7, 2022

Record last verified: 2022-03

Locations

CA (5); US (26)