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

Decision Making Clinical Trial

Official title:

Effects of PF-06412562 on Value-based Decision-making in Healthy Individuals: a Mono-center, Randomized, Placebo Controlled, Double-blind Study (Phase I)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03181841
• Other study ID #: PHA-16-D1AGO-01
• Status: Completed
• Phase: Phase 1
• Start date: May 8, 2017
• Est. completion date: December 20, 2017

Study information

• Verified date: November 2020
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: December 20, 2017
• Est. primary completion date: December 20, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

• Decision Making

Intervention

Drug:
• PF-06412562
double-blind oral intake of single doses of the aforementioned drug or placebo
• Placebo
double-blind oral intake of single doses of the aforementioned drug or placebo

Locations

Country	Name	City	State
Switzerland	University Hospital Zurich, Dept. of Clinical Pharmacology and Toxicology	Zurich

Sponsors (2)

Lead Sponsor	Collaborator
University of Zurich	Pfizer

Country where clinical trial is conducted

Switzerland, 

References & Publications (2)

Soutschek A, Gvozdanovic G, Kozak R, Duvvuri S, de Martinis N, Harel B, Gray DL, Fehr E, Jetter A, Tobler PN. Dopaminergic D(1) Receptor Stimulation Affects Effort and Risk Preferences. Biol Psychiatry. 2020 Apr 1;87(7):678-685. doi: 10.1016/j.biopsych.20 — View Citation

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 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma concentrations of PF-06412562		blood sampling 4 hours and 8 hours after the study drug intake.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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	Incidence of treatment-emergent adverse events (safety and tolerability of PF-06412562)	continuous assessment of adverse events by non-leading questions, repeated safety laboratory tests, repeated ECGs, repeated control of vital parameters.	throughout the study and up to 1 week after study drug intake.