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

NCT02017730 | Completed Phase 1

• 1 other identifier: IM136-106
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Immunology

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• 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

Study Arms (4)

Part 1: [11C]BMT-136088 (Safety Study)

EXPERIMENTAL

Single PET SCAN with single bolus injection of \[11C\]BMT-136088

Drug: [11C]BMT-136088

Part 2: [11C]BMT-136088 (Test/Retest study)

EXPERIMENTAL

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

Part 3: BMS-986020+[11C]BMT-136088 (Receptor Occupancy study)

EXPERIMENTAL

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

Part 4: [11C]BMT-136088 (Tissue Distribution study)

EXPERIMENTAL

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

Interventions

BMS-986020 DRUG

Part 3: BMS-986020+[11C]BMT-136088 (Receptor Occupancy study)

[11C]BMT-136088 DRUG

Part 1: [11C]BMT-136088 (Safety Study); Part 2: [11C]BMT-136088 (Test/Retest study); Part 3: BMS-986020+[11C]BMT-136088 (Receptor Occupancy study); Part 4: [11C]BMT-136088 (Tissue Distribution study)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (1)

Yale Pet Center

New Haven, Connecticut, 06520, United States

Location

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2013
• First Posted: December 23, 2013
• Study Start: January 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: July 7, 2015

Record last verified: 2015-07

Locations

US (1)