A Phase 1, Randomized, Double-blind, Placebo Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 786 in Healthy Subjects and Subjects With Obesity
Overview
- Phase
- Phase 1
- Intervention
- AMG 786
- Conditions
- Obesity
- Sponsor
- Amgen
- Enrollment
- 65
- Locations
- 3
- Primary Endpoint
- Number of Participants who Experience a Treatment-emergent Adverse Event (TEAE)
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief Summary
The primary objective of this study is to assess the safety and tolerability of AMG 786 as single or multiple doses in healthy and obese participants.
Detailed Description
The 4th Multiple Ascending Dose cohort was not started.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant has provided informed consent/assent prior to initiation of any study-specific activities/procedures
- •Age 18 to 65 years at the time of signing the informed consent
- •Female participants must be of non-childbearing potential (as described below)
- •Postmenopausal is defined as:
- •Age of ≥ 55 years with no menses for at least 12 months; OR
- •Age \< 55 years with no menses for at least 12 months AND with a follicle-stimulating hormone (FSH) level \> 40 IU/L or according to the definition of "postmenopausal range" for the laboratory involved; OR
- •History of hysterectomy; OR
- •History of bilateral oophorectomy
- •Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and Electrocardiograms (ECGs) on day -1 (Part A) and day -1 (Part B) and screening
- •Body Mass Index must be between 18 and \< 25 kg/m\^2 for healthy participants and between ≥ 25 and ≤ 32.0 kg/m\^2 for otherwise healthy participants with obesity
Exclusion Criteria
- •Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years
- •History or clinical evidence of diabetes mellitus, including a fasting glucose ≥ 125 mg/dl (6.9 mmol/L) and/or HbA1c ≥ 6.5%
- •Triglycerides ≥ 5.65 mmol/L (ie, 500 mg/dL) at screening
- •Hepatic liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or total bilirubin levels \> 1.5 times the upper limit of normal (ULN) at screening. Participants with suspected or diagnosed Gilbert's disease will be excluded from the study.
- •History or clinical evidence of bleeding diathesis or any coagulation disorder, including prothrombin time (PT), activated partial thromboplastin time (APTT), International normalized ratio (INR) or platelet count outside of the laboratory's normal reference range unless interpreted as not clinically significant by the investigator in consultation with the medical monitor at screening.
- •History of gastrointestinal (GI) abnormality that could affect GI motility (including small bowel or colonic resection, inflammatory bowel disease, irritable bowel disease, and colon or GI tract cancer)
- •Untreated or uncontrolled hypothyroidism/hyperthyroidism defined as thyroid-stimulating hormone (TSH) value outside normal range
- •A corrected QT interval at screening of \> 450 msec in males or \> 470 msec in females or history of long QT syndrome
- •History of coronary artery disease or congestive heart failure
- •Participants with a history of renal impairment or renal disease and/or estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m\^2
Arms & Interventions
Part A: Single Ascending Dose Cohorts
Participants in 4 cohorts will receive either AMG 786 or placebo in Single Ascending Doses.
Intervention: AMG 786
Part A: Single Ascending Dose Cohorts
Participants in 4 cohorts will receive either AMG 786 or placebo in Single Ascending Doses.
Intervention: Placebo
Part A: Food Effect Cohort
Participants in the food effect cohort (FEC) will receive 1 of 2 AMG 786 in 1 of two sequences. Participants in Sequence 1 will receive a dose of AMG 786 on day 1 under fed conditions followed by a 10-day washout period and another dose of AMG 786 on day 11 under fasted conditions. Participants in Sequence 2 in the FEC cohort will receive the first dose on day 1 under fasted conditions and the second dose on day 11 under fed conditions.
Intervention: AMG 786
Part A: Food Effect Cohort
Participants in the food effect cohort (FEC) will receive 1 of 2 AMG 786 in 1 of two sequences. Participants in Sequence 1 will receive a dose of AMG 786 on day 1 under fed conditions followed by a 10-day washout period and another dose of AMG 786 on day 11 under fasted conditions. Participants in Sequence 2 in the FEC cohort will receive the first dose on day 1 under fasted conditions and the second dose on day 11 under fed conditions.
Intervention: Placebo
Part B: Multiple Ascending Dose Cohorts
Participants in 4 cohorts will receive either AMG 786 or placebo in Multiple Ascending Doses.
Intervention: AMG 786
Part B: Multiple Ascending Dose Cohorts
Participants in 4 cohorts will receive either AMG 786 or placebo in Multiple Ascending Doses.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants who Experience a Treatment-emergent Adverse Event (TEAE)
Time Frame: Day 1 through end of study (approximately 40 days)
Any clinically significant changes in vital signs, 12-lead electrocardiograms (ECGs) and clinical laboratory tests will be recorded as TEAEs.
Secondary Outcomes
- Maximum Observed Concentration (Cmax) of AMG 786(Day 1 through end of study (approximately 40 days))
- AUC of Metabolite M5(Day 1 through end of study (approximately 40 days))
- Time of Maximum Observed Concentration (Tmax) of AMG 786(Day 1 through end of study (approximately 40 days))
- Area Under the Concentration-time Curve (AUC) of AMG 786(Day 1 through end of study (approximately 40 days))
- Cmax of Metabolite M5(Day 1 through end of study (approximately 40 days))
- Tmax of Metabolite M5(Day 1 through end of study (approximately 40 days))