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

NCT03181841 | Completed Phase 1

• 1 other identifier: PHA-16-D1AGO-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Decision Making

Outcome Measures

Primary Outcomes (6)

• Change from baseline in a delay discounting task.

  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.

  1-3 weeks before (= baseline), 5 hours after, and approx. 1 week after drug intake.

• Change from baseline in a risk discounting task.

  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.

  1-3 weeks before (= baseline), 5 hours after, and approx. 1 week after drug intake.

• Effect of PF-06412562 on an effort discounting task (compared to placebo).

  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.

  5 hours after drug intake.

• Effect of PF-06412562 on the Pavlovian to instrumental transfer task (compared to placebo).

  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.

  5 hours after drug intake.

• Effect of PF-06412562 on an exploration / exploitation task (compared to placebo).

  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.

  5 hours after drug intake.

• Effect of PF-06412562 on a probabilistic reversal learning task (compared to placebo).

  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.

  5 hours after drug intake.

Secondary Outcomes (1)

• Incidence of treatment-emergent adverse events (safety and tolerability of PF-06412562)

  throughout the study and up to 1 week after study drug intake.

Other Outcomes (1)

• Plasma concentrations of PF-06412562

  blood sampling 4 hours and 8 hours after the study drug intake.

Study Arms (4)

Active dose 1

EXPERIMENTAL

Single dose of PF-06412562 in low dosage strength

Drug: PF-06412562

Active dose 2

EXPERIMENTAL

Single dose of PF-06412562 in medium dosage strength

Drug: PF-06412562

Active dose 3

EXPERIMENTAL

Single dose of PF-06412562 in higher dosage strength

Drug: PF-06412562

Placebo

PLACEBO COMPARATOR

Single dose of placebo

Drug: Placebo

Interventions

PF-06412562 DRUG

double-blind oral intake of single doses of the aforementioned drug or placebo

Active dose 1; Active dose 2; Active dose 3

Placebo DRUG

double-blind oral intake of single doses of the aforementioned drug or placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Normal or corrected-to-normal vision
• 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.

Sponsors & Collaborators

• University of Zurich: lead
• Pfizer: collaborator

Study Sites (1)

University Hospital Zurich, Dept. of Clinical Pharmacology and Toxicology

Zurich, CH-8091, Switzerland

Location

Related Publications (3)

• Soutschek A, Gvozdanovic G, Kozak R, Duvvuri S, de Martinis N, Harel B, Gray DL, Fehr E, Jetter A, Tobler PN. Dopaminergic D1 Receptor Stimulation Affects Effort and Risk Preferences. Biol Psychiatry. 2020 Apr 1;87(7):678-685. doi: 10.1016/j.biopsych.2019.09.002. Epub 2019 Sep 12.

  PMID: 31668477 RESULT

• Soutschek A, Kozak R, de Martinis N, Howe W, Burke CJ, Fehr E, Jetter A, Tobler PN. Activation of D1 receptors affects human reactivity and flexibility to valued cues. Neuropsychopharmacology. 2020 Apr;45(5):780-785. doi: 10.1038/s41386-020-0617-z. Epub 2020 Jan 21.

  PMID: 31962344 RESULT

• Soutschek A, Tobler PN. A process model account of the role of dopamine in intertemporal choice. Elife. 2023 Mar 8;12:e83734. doi: 10.7554/eLife.83734.

  PMID: 36884013 DERIVED

Study Officials

• Philippe Tobler, Prof. Dr.

  University of Zurich, Dept. of Economics

  STUDY DIRECTOR

• Alexander Jetter, MD

  University of Zurich

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 12, 2017
• First Posted: June 9, 2017
• Study Start: May 8, 2017
• Primary Completion: December 20, 2017
• Study Completion: December 20, 2017
• Last Updated: November 5, 2020

Record last verified: 2020-11

Locations

CH (1)