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

NCT ID: NCT03181841

Last Updated: 2020-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-08
• Study Completion Date: 2017-12-20

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Active dose 1

Single dose of PF-06412562 in low dosage strength

Group Type: EXPERIMENTAL

PF-06412562

Intervention Type: DRUG

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

Active dose 2

Single dose of PF-06412562 in medium dosage strength

Group Type: EXPERIMENTAL

PF-06412562

Intervention Type: DRUG

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

Active dose 3

Single dose of PF-06412562 in higher dosage strength

Group Type: EXPERIMENTAL

PF-06412562

Intervention Type: DRUG

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

Placebo

Single dose of placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

PF-06412562

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe Tobler, Prof. Dr.

Role: STUDY_DIRECTOR

University of Zurich, Dept. of Economics

Alexander Jetter, MD

Role: PRINCIPAL_INVESTIGATOR

University of Zurich

Locations

University Hospital Zurich, Dept. of Clinical Pharmacology and Toxicology

Zurich, , Switzerland

Countries

Switzerland

References

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.

Reference Type: RESULT

PMID: 31668477 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31962344 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36884013 (View on PubMed)

Other Identifiers

PHA-16-D1AGO-01

Identifier Type: -

Identifier Source: org_study_id