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

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

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.

Study Overview

• Status: Completed
• Conditions: Immunology
• Intervention / Treatment: Drug: BMS-986020; Drug: [11C]BMT-136088

Detailed Description

End point Classification: Pharmacokinetics/Pharmacodynamics

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale PET Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: [11C]BMT-136088 (Safety Study); Single PET SCAN with single bolus injection of [11C]BMT-136088	Drug: [11C]BMT-136088
Experimental: Part 2: [11C]BMT-136088 (Test/Retest study); 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
Experimental: Part 3: BMS-986020+[11C]BMT-136088 (Receptor Occupancy study); 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; Drug: [11C]BMT-136088
Experimental: Part 4: [11C]BMT-136088 (Tissue Distribution study); 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: December 17, 2013
• First Submitted That Met QC Criteria: December 17, 2013
• First Posted (Estimate): December 23, 2013

Study Record Updates

• Last Update Posted (Estimate): July 7, 2015
• Last Update Submitted That Met QC Criteria: July 3, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Other Study ID Numbers: IM136-106