PF-04995274 and Emotional Processing in Treatment Resistant Depression

NCT03515733 | Completed Phase 1

• 1 other identifier: PF04995274 Study 2 RESTART
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test whether seven days adjunctive administration of a serotonin receptor subtype 4 (5HT4) agonist called PF-04995274 has positive effects on emotional processing and non-emotional cognition in medicated, treatment-resistant depressed patients compared to placebo.

Conditions

Depression, Unipolar; Treatment Resistant Depression

Outcome Measures

Primary Outcomes (2)

• Facial Expression Recognition Task (FERT)

  Facial expressions of basic emotions (happiness, fear, anger, disgust, sadness, surprise) are displayed on the screen and participants are asked to correctly classify them. Each emotion is presented at different intensity levels. Responses are made via a button-press and accuracy and reaction time are recorded.

  Completed on Day 7

• Auditory Verbal Learning Task (AVLT)

  Accuracy of recall on the auditory verbal learning task

  Completed on Day 7

Secondary Outcomes (2)

• Emotional Memory Task

  Completed on Day 7

• Probabilistic Instrumental Learning Task (PILT)

  Completed on Day 7

Study Arms (2)

PF-04995274

EXPERIMENTAL

PF-04995274, three x 5mg tablet (15mg total), once daily for 7-9 days

Drug: PF-04995274

Placebo

PLACEBO COMPARATOR

3 placebo tablets, once daily for 7-9 days

Drug: Placebo Oral Tablet

Interventions

PF-04995274 DRUG

PF-04995274 tablets

PF-04995274

Placebo Oral Tablet DRUG

Placebo tablet, identical appearance to experimental tablet

Placebo

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female;
• Aged 18-65 years;
• Willing and able to give informed consent for participation in the study;
• Sufficiently fluent English to understand and complete the tasks;
• Registered with a GP and consents to GP being informed of participation in study;
• Participants need to meet a number of concurrent clinical criteria:
• Current criteria for Major Depressive Disorder \[as determined by the Structured Clinical interview for DSM-V (SCID)\];
• Failure within the current depressive episode to respond clinically to at least one course of antidepressant therapy, each given at a therapeutic dose for at least four weeks \[as determined by use of the MGH Antidepressant Treatment Response Questionnaire (ATRQ)\];
• Currently taking an antidepressant, which must be either a Selective Serotonin Reuptake Inhibitor (SSRI) - with the exception of fluoxetine, paroxetine or fluvoxamine - or a Serotonin-norepinephrine reuptake inhibitor (SNRI) ; Participants currently taking excluded medications can be switched to sertraline or citalopram;
• Participants engaging in sex with a risk of pregnancy must agree to use a highly effective method of contraception from Screening Visit until 30 days after receiving study medication treatment, and male participants must not donate sperm.

You may not qualify if:

• History of or current DSM-V bipolar disorder, schizophrenia or eating disorders. Participants who fulfil current criteria for other comorbid disorders may still be entered into the study, if, in the opinion of the Investigator, the psychiatric diagnosis will not compromise safety or affect data quality;
• First-degree relative with a diagnosis of Bipolar Disorder type 1;
• Participants currently taking strong cytochrome P450 (CYPs) enzymes inhibitors, such as fluoxetine, paroxetine or fluvoxamine (in order to avoid drug-drug interactions);
• Participants currently taking psychotropic medications which in the opinion of the investigator may interfere with the safety of the participant or the scientific integrity of the study;
• Participants who have previously failed a combination/augmentation therapy (i.e., therapy with the combination of two or more pharmacological agents) for the treatment of depression, which in the opinion of the Investigator may reduce the likelihood of responding;
• Electroconvulsive therapy for the treatment of the current episode of depression;
• Participants undergoing any form of face-to-face structured psychological treatment during the study;
• Clinically significant abnormal values for liver function tests, clinical chemistry, urine drug screen, blood pressure measurement and ECG. A participant with a clinical abnormality or parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures;
• History of stimulant abuse (lifetime; e.g. amphetamine, cocaine), or of alcohol abuse within one year or of alcohol dependence within the lifetime;
• History of, or current medical conditions which in the opinion of the investigator may interfere with the safety of the participant or the scientific integrity of the study, including epilepsy/seizures, brain injury, severe hepatic or renal disease, severe gastro-intestinal problems, Central Nervous System (CNS) tumors, severe neurological problems (like Parkinson's Disease; blackouts requiring hospitalisation);
• Clinically significant risk of suicide;
• Current pregnancy (as determined by urine pregnancy test taken during Screening and First Dose Visits), breastfeeding or planning a pregnancy during the course of the study;
• Participant not willing to use a suitable method of contraception for 30 days after receiving study medication treatment;
• Participants with Body Mass Index (BMI - kg/m2) outside the 18 - 36 range at the Screening Visit;
• Night-shift working or recent travel involving significant change of timezones;

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

University of Oxford

Oxford, Oxfordshire, OX3 7JX, United Kingdom

Location

Related Publications (1)

• Murphy SE, de Cates AN, Gillespie AL, Godlewska BR, Scaife JC, Wright LC, Cowen PJ, Harmer CJ. Translating the promise of 5HT4 receptor agonists for the treatment of depression. Psychol Med. 2021 May;51(7):1111-1120. doi: 10.1017/S0033291720000604. Epub 2020 Apr 3.

  PMID: 32241310 DERIVED

MeSH Terms

Conditions

Depressive Disorder; Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Study Officials

• Catherine Harmer

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly allocated to one of two groups (PF-04995264 or placebo) and receive their allocated study medication for 7 days.

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 4, 2018
• Study Start: May 31, 2018
• Primary Completion: July 26, 2022
• Study Completion: July 26, 2022
• Last Updated: November 4, 2022

Record last verified: 2022-07

Locations

GB (1)