Clinical trial NCT01312922: Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in Major Depressive Disorder (MDD)
Official title: Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in the Treatment of Moderate to Severe Major Depressive Disorder (MDD): a Randomized, Double-blind Phase III Study of 10 Weeks
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Lead sponsor: PharmaNeuroBoost N.V.
Sponsor class: INDUSTRY
First posted: 2011-03-11
Enrollment: 555
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Early and Sustained (Antidepressant) Response (ESR) Rate
timeFrame: From (end of) Week 2 visit to (end of) Week 6 visit
Secondary outcomes:
measure: Change From Baseline in Total MADRS Score at Week 6
timeFrame: From Baseline (Day 1) to (end of) Week 6
measure: Change From Baseline in Total SDS Score at Week 6
timeFrame: From Baseline (Day 1) to (end of) Week 6 visit
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Site 103
state: California
city: National City
country: United States
facility: Site 101
state: California
city: Riverside
country: United States
facility: Site 113
state: California
city: San Diego
country: United States
facility: Site 106
state: California
city: San Diego
country: United States
facility: Site 116
state: California
city: Fort Myers
country: United States
facility: Site 112
state: Florida
city: Miami
country: United States
facility: Site 135
state: Florida
city: Winter Park
country: United States
facility: Site 108
state: Florida
city: Atlanta
country: United States
facility: Site 133
state: Georgia
city: Smyrna
country: United States
facility: Site 128
state: Georgia
city: Libertyville
country: United States
facility: Site 132
state: Illinois
city: Schaumburg
country: United States
facility: Site 117
state: Illinois
city: Baltimore
country: United States
facility: Site 110
state: Maryland
city: Flowood
country: United States
facility: Site 109
state: Mississippi
city: New York
country: United States
facility: Site 115
state: New York
city: Beachwood
country: United States
facility: Site 126
state: Ohio
city: Cincinnati
country: United States
facility: Site 127
state: Ohio
city: Middleburg Heights
country: United States
facility: Site 124
state: Ohio
city: Allentown
country: United States
facility: Site 105
state: Pennsylvania
city: Media
country: United States
facility: Site 123
state: Pennsylvania
city: Philadelphia
country: United States
facility: Site 122
state: Pennsylvania
city: Austin
country: United States
facility: Site 119
state: Texas
city: Dallas
country: United States
facility: Site 104
state: Texas
city: Wichita Falls
country: United States
facility: Site 102
state: Texas
city: Kirkland
country: United States
facility: Site 107
state: Washington
city: Seattle
country: United States
facility: Site 134
state: Washington
city: Kelowna
country: Canada
facility: Site 201
state: British Columbia
city: Penticton
country: Canada
facility: Site 202
state: British Columbia
city: Chatham
country: Canada
facility: Site 205
state: Ontario
city: Mississauga
country: Canada
facility: Site 203
state: Ontario
city: Mississauga
country: Canada
facility: Site 204
state: Ontario
Study officials:
affiliation: Director, Mood and Anxiety Section; 3535 Market Street, Suite 670; Philadelphia, PA 19104-3309, United States of America
name: Michael E Thase, MD
role: STUDY_CHAIR
affiliation: Bezirkskrankenhaus Augsburg Klinik für Psychiatrie, Psychotherapie und Psychosomatik Dr.-Mack-Straße 1 D-86156 Augsburg, Germany
name: Max Schmauss, MD
role: STUDY_CHAIR
affiliation: Pharmaneuroboost N.V. Alkerstraat 30A B-3570 Alken, Belgium
name: Philippe Lemmens, PhD
role: STUDY_DIRECTOR
References: