Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in Major Depressive Disorder (MDD)
Information source: PharmaNeuroBoost N.V.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Major Depressive Disorder
Intervention: PNB01 fixed dose combination of pipamperone and citalopram (Drug); Citalopram (Drug); Pipamperone (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: PharmaNeuroBoost N.V. Official(s) and/or principal investigator(s): Michael E Thase, MD, Study Chair, Affiliation: Director, Mood and Anxiety Section; 3535 Market Street, Suite 670; Philadelphia, PA 19104-3309, United States of America Max Schmauss, MD, Study Chair, Affiliation: Bezirkskrankenhaus Augsburg Klinik für Psychiatrie, Psychotherapie und Psychosomatik Dr.-Mack-Straße 1 D-86156 Augsburg, Germany Philippe Lemmens, PhD, Study Director, Affiliation: Pharmaneuroboost N.V. Alkerstraat 30A B-3570 Alken, Belgium
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Early and Sustained (antidepressant) Response (ESR) rate
Secondary outcome: Change from baseline in total MADRS score at Week 6Change from baseline in total SDS score at Week 6
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Site 201, Kelowna, British Columbia, Canada
Site 202, Penticton, British Columbia, Canada
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 Meyers, 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 205, Chatham, Ontario, Canada
Site 203, Mississauga, Ontario, Canada
Site 204, Mississauga, Ontario, Canada
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
Additional Information
Starting date: September 2011
Last updated: November 18, 2014
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