Major Depressive DisorderPhase 3NCT01312922

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

A Phase 3 study testing PNB01 fixed dose combination of pipamperone and citalopram, Citalopram and Pipamperone in people with Major Depressive Disorder, run by PharmaNeuroBoost N.V. at 31 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Major Depressive Disorder
What is being tested?: PNB01 fixed dose combination of pipamperone and citalopram, Citalopram and Pipamperone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 555 participants
Where: 31 sitesin 2 countries
Study dates: Sep 2011to Dec 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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).

Show all 18Show fewer

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).
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).
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.
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.
Known hypersensitivity to any of the study drugs

Trial locations and contacts

31 sites in 2 countries.

Country

City, postcode or hospital

31 sites in 2 countries

United States26 sites

Site 105
Allentown, Pennsylvania
Site 133
Atlanta, Georgia
Site 119
Austin, Texas
Site 110
Baltimore, Maryland
Site 126
Beachwood, Ohio
Site 127
Cincinnati, Ohio
Site 104
Dallas, Texas
Site 109
Flowood, Mississippi
Site 112
Fort Myers, Florida
Site 103
Glendale, California
Site 107
Kirkland, Washington
Site 132
Libertyville, Illinois
Site 123
Media, Pennsylvania
Site 135
Miami, Florida
Site 124
Middleburg Heights, Ohio
Site 101
National City, California
Site 115
New York, New York
Site 122
Philadelphia, Pennsylvania
Site 113
Riverside, California
Site 106
San Diego, California
Site 116
San Diego, California
Site 117
Schaumburg, Illinois
Site 134
Seattle, Washington
Site 128
Smyrna, Georgia
Site 102
Wichita Falls, Texas
Site 108
Winter Park, Florida

Other trials in United States

Canada5 sites

Site 205
Chatham, Ontario
Site 201
Kelowna, British Columbia
Site 203
Mississauga, Ontario
Site 204
Mississauga, Ontario
Site 202
Penticton, British Columbia

Other trials in Canada

About this study

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

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

Read the 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
Being tested: PNB01 fixed dose combination of pipamperone and citalopram, Citalopram, Pipamperone
Medical subject headings: Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PNB01 fixed dose combination of pipamperone and citalopramDrug
oral once daily administration
CitalopramDrug
oral once daily administration
PipamperoneDrug
oral once daily administration

Study groups in NCT01312922
Study group	Role	What they receive
PNB01	Experimental	oral, once daily administration Receives: Drug: PNB01 fixed dose combination of pipamperone and citalopram
citalopram	Active comparator	oral, once daily administration Receives: Drug: Citalopram
pipamperone	Sham comparator	oral, once daily administration Receives: Drug: Pipamperone

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
Change from baseline in total score on the Montgomery-Asberg Depression Rating Scale (MADRS) after 6 weeks of study treatment as assessed by the patient using an Interactive Voice Response System (IVRS) via telephone
The MADRS scale is a widely used and well-validated 10-item diagnostic questionnaire designed to measure the severity of depressive episodes in patients with mood disorders. The 10 items are all rated on a scale from 0 to 6 (resulting in a maximum total score of 60 points) and include 'apparent sadness', 'reported sadness', 'inner tension', 'reduced sleep', 'reduced appetite', 'concentration difficulties', 'lassitude', 'inability to feel', 'pessimistic thoughts' and 'suicidal thoughts'. Higher scores indicative of greater depressive symptomology.
Measured: From Baseline (Day 1) to (end of) Week 6
Change From Baseline in Total SDS Score at Week 6
Change from baseline in total score on the Sheehan Disability Scale (SDS) after 6 weeks of study treatment as assessed by the patient using an Interactive Voice Response System (IVRS) via telephone
The SDS is a generic brief self-report tool that was developed to assess functional impairment in three inter-related domains; 1) work or school, 2) social life and 3) family life. The patient rates the extent to which work/school, social life and home life or family responsibilities are impaired by his or her symptoms on a 10-point visual analog scale. Total scores range from a minimum of 0 to a maximum of 30 (0 unimpaired, 30 highly impaired).
Measured: From Baseline (Day 1) to (end of) Week 6 visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2011Dec 2012

First posted11 Mar 2011 (estimated)
Study startSep 2011
Primary completionNov 2012
Study completionDec 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 555 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01312922
Sponsor's protocol ID: PNB01-C301
Other IDs: 2011-001190-11
Status last verified: Mar 2022
First submitted: 8 Mar 2011
Last updated: 7 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 7 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01312922
Acronym / sponsor ID: PNB01-C301
Conditions: Major Depressive Disorder
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 555 participants (actual)
Lead sponsor: PharmaNeuroBoost N.V.Industry (pharma, biotech, devices)
Study start: Sep 2011
Primary completion: Nov 2012 (actual)
Study completion: Dec 2012 (actual)
First posted: 11 Mar 2011 (estimated)
Results: Posted 7 Apr 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
PNB01	Experimental	Drug: PNB01 fixed dose combination of pipamperone and citalopramoral, once daily administration
citalopram	Active comparator	Drug: Citalopramoral, once daily administration
pipamperone	Sham comparator	Drug: Pipamperoneoral, once daily administration

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (18 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PNB01 fixed dose combination of pipamperone and citalopramoral once daily administration	Drug	PNB01
Citalopramoral once daily administration	Drug	citalopram
Pipamperoneoral once daily administration	Drug	pipamperone

Primary outcome

Early and Sustained (Antidepressant) Response (ESR) Rate
Time frame: From (end of) Week 2 visit to (end of) Week 6 visit
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.

2 secondary outcomes

Change From Baseline in Total MADRS Score at Week 6
Time frame: From Baseline (Day 1) to (end of) Week 6
Change From Baseline in Total SDS Score at Week 6
Time frame: From Baseline (Day 1) to (end of) Week 6 visit

Results and safety

Results posted to the registry on 7 Apr 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PNB01	185	117
Citalopram	185	131
Pipamperone	185	135

Primary outcome: Early and Sustained (Antidepressant) Response (ESR) Rate

Time frame: From (end of) Week 2 visit to (end of) Week 6 visit. Count of participants. Unit: Participants

Measure	PNB01 n = 176	Citalopram n = 174	Pipamperone n = 181
Value	17	17	17

PNB01 vs Citalopram: Odds Ratio (OR): 0.987 (95% CI 0.456 to 2.140), p = 1.000, Fisher Exact
PNB01 vs Pipamperone: Odds Ratio (OR): 1.031 (95% CI 0.476 to 2.233), p = 1.000, Fisher Exact

Population analysed: Full Analysis Set (FAS): The FAS consists of all patients who are randomized and were administered at least one dose of trial medication, as assessed from pill counting. Patients will be analyzed according to the treatment group to which they were randomized (intention-to-treat principle), irrespective of the study treatment received.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 10 weeks + follow-up 1 week. Other adverse events reported at 4% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PNB01	3 of 185 (1.6%)	127 of 185 (68.6%)	0 of 185
Citalopram	4 of 185 (2.2%)	131 of 185 (70.8%)	0 of 185
Pipamperone	1 of 185 (0.5%)	118 of 185 (63.8%)	0 of 185

Limitations and caveats (from the sponsor): 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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michael E Thase, MD study chair

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

Max Schmauss, MD study chair

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

Philippe Lemmens, PhD study director

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

31 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Early and Sustained (Antidepressant) Response (ESR) Rate (time frame: From (end of) Week 2 visit to (end of) Week 6 visit). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01312922.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2022.