To Evaluate The Relationship Between Plasma Drug Levels And Receptor Binding in Lung Using PET (Positron Emission Tomography) In Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of a novel positron emission tomography (PET) tracer [11C]BMT-136088 in healthy adult subjects for measurement of availability of Lysophosphatidic Acid (LPA1) receptors in the human lung and to use this tracer to assess LPA1 receptor occupancy using [11C]BMT-136088 in the human lung following oral administration of Bristol Myers Squibb (BMS)-986020.

Detailed Description
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End point Classification: Pharmacokinetics/Pharmacodynamics

Official Title
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An Open-Label Study To Evaluate The Safety and Tolerability Of A Novel LPA1 Receptor Positron Emission Tomography (PET) Ligand [11C]BMT-136088 And To Assess Receptor Occupancy In Human Lung Following Oral Administration Of BMS-986020 In Healthy Subjects

Conditions
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Immunology

Intervention / Treatment
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* Drug: BMS-986020
* Drug: [11C]BMT-136088


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Body weight at least 50kg (110lbs), Body Mass Index (BMI) within 19 to 32 kg/m2, inclusive Must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests Negative hepatitis panel and negative human immunodeficiency virus (HIV)antibody screens Exclusion Criteria: Any history or presence of clinically significant respiratory, Gastro Intestinal (GI), renal, hepatic, pancreatic, hematological, neurological (including history of seizure), cardiovascular, psychiatric (including known addictive disorders), musculoskeletal, genitourinary, immunological, or dermatological disorders, including all cancers Any acute or chronic condition that, in the opinion of the investigator in consultation with the BMS Medical Monitor, could jeopardize the subject's safety, tolerability, or pharmacokinetics of the BMS-986020 Any major surgery within 4 weeks of study drug administration Existence of a cold, upper respiratory tract infection, or fever within 5 days prior to check-in Presence or history of any abnormality or illness that may affect absorption, distribution, metabolism or elimination of the study drug Donation of blood or plasma (exclude the screening visit) within 2 months prior to check in through end of synthesis (EOS), inclusive

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: [11C]BMT-136088 (Safety Study)<br>Single PET SCAN with single bolus injection of [11C]BMT-136088 | Drug: [11C]BMT-136088<br> <br> |
| Experimental: Part 2: [11C]BMT-136088 (Test/Retest study)<br>Single PET SCAN with Intravenous (IV) bolus plus infusion of [11C]BMT-136088 followed by a re-test PET scan (approximately 6 hours apart) with IV bolus plus infusion of [11C]BMT-136088 | Drug: [11C]BMT-136088<br> <br> |
| Experimental: Part 3: BMS-986020+[11C]BMT-136088 (Receptor Occupancy study)<br>BMS-986020 Tablets or Oral Solution of 4 dose levels from from the 6 dose levels of (50 mg, 150 mg, 300 mg, 600 mg, 1200 mg and 1500 mg) and 3 PET SCANS (Pre-Dose, Post-Dose1, Post-Dose2) with bolus plus infusion of [11C]BMT-136088 | Drug: BMS-986020<br> <br> Drug: [11C]BMT-136088<br> <br> |
| Experimental: Part 4: [11C]BMT-136088 (Tissue Distribution study)<br>Single PET SCAN with [11C]BMT-136088 to evaluate additional tracer uptake sites in humans other than the lung, such as heart, kidney, liver, gallbladder, etc. | Drug: [11C]BMT-136088<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall safety and tolerability of novel tracer [11C]BMT-136088 | The following safety endpoints will be considered, the incidence of adverse events (AEs), serious AEs, AEs leading to discontinuation from the study, and death as well as marked abnormalities in clinical laboratory tests, vital sign measurements, electrocardiograms (ECGs), and physical examinations occurring from screening up to study discharge. | Approximately up to 90 days | 
| Lung LPA1 percentage receptor occupancy of BMS-986020 | Assessed by [11C]BMT-136088 tracer lung volume of distribution (VT) before and after single oral dose of BMS-986020. | Up to 2 days post BMS-986020 administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exposure-response relationship between lung LPA1 percentage receptor occupancy and BMS-986020 plasma concentration. |  | Up to 48 hr postdose (Approximately up to Day 3) | 
| Maximum observed concentration (Cmax) of BMS-986020 |  | 13 timepoints up to Day 3 | 
| Time of maximum observed concentration (Tmax) of BMS-986020 |  | 13 timepoints up to Day 3 | 
| Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-986020 |  | 13 timepoints up to Day 3 | 
| Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986020 |  | 13 timepoints up to Day 3 | 
| Half life (T-HALF) of BMS-986020 |  | 13 timepoints up to Day 3 | 
| Safety of single oral dose of BMS-986020 where [11C]BMT-136088 is administered to healthy subjects | Safety based on incidence of AEs, serious AEs, AEs leading to discontinuation, and death as well as marked abnormalities in clinical laboratory tests, vital sign measurements, ECGs, and physical examinations | Approximately up to 90 days |