PET Study to Determine the Relationship Between Plasma Concentrations and Muscarinic Type 1 Receptor (M1AChR) Occupancy of PIPE-307 in Healthy Volunteers

Study Overview
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Brief Summary
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This is a Phase 1, single-center, open-label, adaptive-design PET study to investigate the occupancy of brain muscarinic Type 1 receptors (M1AChR) by PIPE-307 in healthy volunteers.

Detailed Description
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This is a Phase 1, single-center, open-label, adaptive-design study to investigate the occupancy of brain M1AChR after a single oral dose of PIPE-307 in healthy volunteers by positron emission tomography (PET) using the radioligand [11C] PIPE-307. This study will have an adaptive design to adequately evaluate the relationship between PIPE-307 exposure and brain M1AChR occupancy.

Official Title
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A Phase 1, Open-label Study of PIPE-307 to Determine Muscarinic Type I Receptor (M1AChR) Occupancy Parameters by [11C] PIPE-307 PET Imaging in Healthy Volunteers

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: PIPE-307


Participation Criteria
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Eligibility Criteria
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Key Criteria: Normotensive male or female volunteers between 25-65 years old Deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine Key Exclusion Criteria: Clinically relevant abnormal findings at the screening assessments Clinically relevant abnormal medical history or concurrent medical condition Acute or chronic illness Contraindications to MRI, CT, PET, or arterial cannulation procedures Significant exposure to research related radiation or other exposure (defined as ICRP category IIb or no more than 10 mSv) Positive tests for hepatitis B surface antigen (HBsAg) & Hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody Drug or alcohol abuse Smoke more than 10 cigarettes daily Loss of more than 400 mL blood Vital signs or ECGs outside the acceptable range

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PIPE-307<br>Subjects will receive an oral dose of PIPE-307 and 3 intravenous injections of [11C] PIPE- 307. | Drug: PIPE-307<br>* Each dose cohort will receive a single oral dose of PIPE-307. Doses to be tested in subsequent cohorts will be determined by the analysis of the exposure from PK data and the PET scans with [11C] PIPE-307. Subjects will receive an intravenous dose of the radioligand [11C] PIPE-307 prior to PET imaging.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| M1AChR receptor occupancy as determined by regional total volume of distribution (VT) of [11C] PIPE-307 at 24 hours |  | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis