- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04691115
Safety, Tolerability and Pharmacokinetics of AM1476 in Healthy Subjects
AM1476 - A Phase I, Double-blind, Placebo-controlled, Single- and Multiple-oral Dose, Safety, Tolerability, and Pharmacokinetic Study in Healthy Subjects
Study Overview
Detailed Description
Part A (SAD); In the SAD part of the study, single oral doses of AM1476 will be administered in up to 9 sequential groups, each consisting of 8 subjects randomised to recieve either AM1476 or placebo in a 3:1 ratio. The first 2 subjects in each group will be dosed in a sentinel fashion, 1 subject will receive AM1476 and the other will receive placebo as randomised. The SAD part incorporating a 2-period crossover arm for a food-effect evaluation in 2 groups.
Part B (MAD); The MAD part of the study will explore multiple ascending dosing of AM1476 for 10 days. AM1476 will be administered in up to 6 sequential groups, each consisting of 8 subjects randomised to recieve either AM1476 or placebo in a 3:1 ratio.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Leeds, United Kingdom, LS2 9LH
- Covance Clinical Research Unit
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Males or females, of any race, between 18 and 60 years of age, inclusive.
- A body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive.
- In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital non-haemolytic hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at Screening and/or Check-in (Day -1) as assessed by the Investigator (or designee).
- Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed in Appendix 4.
- Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
Exclusion Criteria
- Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
- History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
- History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
Any of the following observed in at least 2 of 3 ECG measurements performed:
- QTcF > 450 msec.
- QRS duration > 110 msec.
- PR interval > 220 msec.
- findings which would make QTc measurements difficult or QTc data uninterpretable.
- Any history of additional risk factors for torsades de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome).
- Any history or current controlled or uncontrolled hypertension or systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg confirmed by repeat measurement.
- History of alcoholism or drug/chemical abuse within 2 years prior to Check-in (Day -1).
- Alcohol consumption of > 21 units per week for males and > 14 units per week for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
- Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at Screening or Check-in (Day -1).
- Positive hepatitis panel and/or positive human immunodeficiency virus test (Appendix 2).
- Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing.
- Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's Wort, within 30 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
- Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
- Use or intend to use slow release medications/products considered to still be active within 14 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator (or designee).
- Use or intend to use any non-prescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator (or designee).
- Use of tobacco- or nicotine-containing products within 3 months prior to Check-in (Day -1) or positive cotinine at Screening or Check-in (Day -1).
- Ingestion of poppy seeds, Seville orange, or grapefruit-containing foods or beverages within 7 days prior to Check-in (Day -1).
- Subjects who are vegetarians, vegans, or are unable to consume the high-fat breakfast (subjects who will participate in a food-effect evaluation [planned to be Group A3] only).
- Receipt of blood products within 2 months prior to Check-in (Day -1).
- Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
- Poor peripheral venous access.
- Have previously completed or withdrawn from this study or any other study investigating AM1476, and have previously received AM1476.
- Subjects who are not willing to minimise or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) following administration of study drug until 2 weeks after the last dose.
- Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part A, Group 1: AM1476 1 mg
Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state
|
AM1476 Capsules
|
Experimental: Part A, Group 2: AM1476 5 mg
Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state
|
AM1476 Capsules
|
Experimental: Part A, Group 3: AM1476 25 mg
Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state
|
AM1476 Capsules
|
Experimental: Part A, Group 4: AM1476 125 mg
Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state
|
AM1476 Capsules
|
Experimental: Part A, Group 5: AM1476 375 mg
Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state
|
AM1476 Capsules
|
Experimental: Part A, Group 6: AM1476 650 mg
Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state
|
AM1476 Capsules
|
Experimental: Part A, Group 7: AM1476 950 mg
Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state
|
AM1476 Capsules
|
Experimental: Part A, Group 8: AM1476 1500 mg
Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state
|
AM1476 Capsules
|
Experimental: Part A, Group 9: AM1476 2400 mg
Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state
|
AM1476 Capsules
|
Placebo Comparator: Part A, Groups 1 to 9: Placebo
Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state
|
Placebo Capsules
|
Experimental: Part B, Group 1: AM1476 100 mg QD
Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state
|
AM1476 Capsules
|
Experimental: Part B, Group 2: AM1476 375 mg BID
Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state
|
AM1476 Capsules
|
Experimental: Part B, Group 3: AM1476 500 mg BID
Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state
|
AM1476 Capsules
|
Placebo Comparator: Part B, Groups 1 to 3: Placebo
Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state
|
Placebo Capsules
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Treatment-Emergent Adverse Events, including abnormal laboratory events
Time Frame: Through study completion, an average of 7 weeks
|
Frequency, severity and seriousness of adverse events (AEs) including physical examination, safety laboratory parameters, vitals signs, body temperature and ECGs will be analyzed.
|
Through study completion, an average of 7 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cmax
Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first dose and 48 hours post last dose
|
maximum plasma concentration
|
SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first dose and 48 hours post last dose
|
Tmax
Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first dose and 48 hours post last dose
|
time to Cmax
|
SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first dose and 48 hours post last dose
|
T½
Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first dose and 48 hours post last dose
|
terminal half-life
|
SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 24 hours post first dose and 48 hours post last dose
|
AUC0-t
Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 12/24 hours post first dose and 48 hours post last dose
|
area under the curve from time 0 to time t
|
SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 12/24 hours post first dose and 48 hours post last dose
|
CL/F
Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 12/24 hours post first dose and 48 hours post last dose
|
apparent total clearance
|
SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 12/24 hours post first dose and 48 hours post last dose
|
Vz/F
Time Frame: SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 12/24 hours post first dose and 48 hours post last dose
|
apparent volume of distribution during the terminal phase
|
SAD: From pre-dose to up to 48 hours post-dose; MAD: From pre-dose to 12/24 hours post first dose and 48 hours post last dose
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 1476-291-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Tolerability
-
National Center for Occupational Health and Infection...VA Office of Research and DevelopmentCompletedTolerability | ComfortUnited States
-
AstraZenecaCompletedTolerabilityUnited States
-
JemincareRecruitingSafety and TolerabilityChina
-
Island PharmaceuticalsBeyond Drug DevelopmentCompletedSafety and TolerabilityAustralia
-
Usona InstituteCompletedPharmacokinetics | Tolerability | SafetyUnited States
-
Damian Pharma AGUniversity Hospital Inselspital, Berne; Covance; Foundation for Therapeutic Research...Completed
-
Repros Therapeutics Inc.CompletedPharmacokinetics | TolerabilityUnited States
-
BioGaia ABCompletedHealthy Volunteers | Tolerability | SafetySweden
-
4TEEN4 Pharmaceuticals GmbHRecruitingPhase 1 Study to Evaluate Safety, Tolerability and Pharmacokinetics/-Dynamics of AK1967 (Procizumab)Safety and TolerabilityNetherlands
-
Alumis IncCompletedSafety and TolerabilityUnited States
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States