Effects of PF-06412562 on Value-based Decision-making in Healthy Individuals

Phase 1

Completed

• Conditions: Decision Making
• Interventions: Drug: PF-06412562; Drug: Placebo

• Registration Number: NCT03181841
• Lead Sponsor: University of Zurich

Brief Summary

Numerous psychiatric and neurodegenerative diseases like schizophrenia, dependency on drugs of abuse, depression and Parkinson's disease are related to motivational and cognitive deficits in value-based decision making, which frequently persist even after a successful pharmacological treatment. According to current neurobiologic models, cortical dopamine D1 receptors play a crucial role in taking value-based decisions. In this study, it will be investigated whether value-based decisions in healthy volunteers can be improved by stimulation of D1-receptors. For this purpose, a newly developed dopamine D1-agonist will be used, which selectively increases the activities of frontal D1- and D5-receptors. In this double-blind, randomized, placebo-controlled study, the effects of different single doses of PF-06412562, a not yet licensed D1-agonist, on value-based decision making will be compared with placebo. The use of different dosage strengths will allow to investigate a potential relationship between the extent of activity of the D1-receptor and its influence on behavioral indices.

Therefore, four parallel groups will be investigated. Each participant takes in a single dose of either PF-06412562 in different doses or placebo. A screening exam will be carried out 1-3 weeks before the drug intake, and a follow-up examination will be carried out approx. 1 week after the drug intake. At all 3 visits in the study centre, several tests for the investigation of value-based decision making will be carried out.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-05-08
• Study First Submitted: 2017-05-12
• Study First Submitted QC: 2017-06-08
• Study First Posted: 2017-06-09
• Primary Completion: 2017-12-20
• Study Completion: 2017-12-20
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-03
• Last Update Posted: 2020-11-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Informed Consent as documented by signature on the informed consent form

• Physically and psychiatrically healthy men and women

• Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days for females and 90 days for males after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children.

• Female subjects of non childbearing potential must meet at least one of the following criteria:

  • Have undergone a documented hysterectomy and/or bilateral oophorectomy;
  • Have medically confirmed ovarian failure or;
  • Achieved post menopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the post menopausal state.

• All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.

• Aged 18-35 years

• Negative pregnancy test (see exclusion criteria)

• Normal or corrected-to-normal vision

Exclusion Criteria (selected):

• Pregnant female subjects; breastfeeding female subjects
• considered to be healthy based on an extensive pre-study screening including anamnesis, physical examination, laboratory investigations, vital signs, ECG, etc.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active dose 1	PF-06412562	Single dose of PF-06412562 in low dosage strength
Active dose 3	PF-06412562	Single dose of PF-06412562 in higher dosage strength
Placebo	Placebo	Single dose of placebo
Active dose 2	PF-06412562	Single dose of PF-06412562 in medium dosage strength

Primary Outcome Measures

Name	Time	Method
Change from baseline in a delay discounting task.	1-3 weeks before (= baseline), 5 hours after, and approx. 1 week after drug intake.	This validated computer-based decision-making test will be filled in by each participant at three time points during the study: 1-3 weeks before, 5 hours after, and approx. 1 week after a single oral intake of 1 out of 3 possible doses of PF-06412562, or matching placebo.
Change from baseline in a risk discounting task.	1-3 weeks before (= baseline), 5 hours after, and approx. 1 week after drug intake.	This validated computer-based decision-making test will be filled in by each participant at three time points during the study: 1-3 weeks before, 5 hours after, and approx. 1 week after a single oral intake of 1 out of 3 possible doses of PF-06412562, or matching placebo. It will be carried out after the test for outcome 1.
Effect of PF-06412562 on an effort discounting task (compared to placebo).	5 hours after drug intake.	This validated computer-based decision-making test will be completed by each participant 5 hours after a single oral intake of 1 out of 3 possible doses of PF-06412562, or matching placebo and after having completed the tests for outcome 1 and 2.
Effect of PF-06412562 on the Pavlovian to instrumental transfer task (compared to placebo).	5 hours after drug intake.	This validated computer-based decision-making task tests Pavlovian acquisition and transfer. It will be carried out by each participant immediately after the test in outcome 3.
Effect of PF-06412562 on an exploration / exploitation task (compared to placebo).	5 hours after drug intake.	This validated computer-based decision-making task tests different aspects of value-based decision making. It will be carried out by each participant immediately after the test in outcome 4.
Effect of PF-06412562 on a probabilistic reversal learning task (compared to placebo).	5 hours after drug intake.	This validated computer-based decision-making task tests different aspects of value-based decision making. It will be carried out by each participant immediately after the test in outcome 5.

Secondary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events (safety and tolerability of PF-06412562)	throughout the study and up to 1 week after study drug intake.	continuous assessment of adverse events by non-leading questions, repeated safety laboratory tests, repeated ECGs, repeated control of vital parameters.

Trial Locations

Locations (1)

University Hospital Zurich, Dept. of Clinical Pharmacology and Toxicology; 🇨🇭 Zurich, Switzerland