Safety, Tolerability and Pharmacokinetics of AM1476 in Healthy Subjects

NCT04691115 | Completed Phase 1 Results DMC

• 1 other identifier: 1476-291-001
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

This is a First in Human (FIH), double-blind, randomised, placebo-controlled study designed to evaluate safety, tolerability and pharmacokinetics (PK) of single and multiple ascending oral doses of AM1476 in healthy subjects.

Conditions

Safety; Tolerability

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events

  A treatment-emergent adverse-event (TEAE) was defined as an adverse event that started during or after first dosing, or started prior to first dosing and increased in severity after first dosing.

  Through study completion, an average of 7 weeks

Secondary Outcomes (12)

• Cmax

  From pre-dose to up to 48 hours post-dose

• Cmax

  Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.

• Tmax

  From pre-dose to up to 48 hours post-dose

• Tmax

  Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.

• T½

  From pre-dose to up to 48 hours post-dose

Study Arms (14)

Part A, Group 1: AM1476 1 mg

EXPERIMENTAL

Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state

Drug: AM1476

Part A, Group 2: AM1476 5 mg

EXPERIMENTAL

Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state

Drug: AM1476

Part A, Group 3: AM1476 25 mg

EXPERIMENTAL

Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state

Drug: AM1476

Part A, Group 4: AM1476 125 mg

EXPERIMENTAL

Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state

Drug: AM1476

Part A, Group 5: AM1476 375 mg

EXPERIMENTAL

Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state

Drug: AM1476

Part A, Group 6: AM1476 650 mg

EXPERIMENTAL

Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state

Drug: AM1476

Part A, Group 7: AM1476 950 mg

EXPERIMENTAL

Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state

Drug: AM1476

Part A, Group 8: AM1476 1500 mg

EXPERIMENTAL

Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state

Drug: AM1476

Part A, Group 9: AM1476 2400 mg

EXPERIMENTAL

Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state

Drug: AM1476

Part A, Groups 1 to 9: Placebo

PLACEBO COMPARATOR

Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state

Drug: Placebo

Part B, Group 1: AM1476 100 mg QD (once daily)

EXPERIMENTAL

Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state

Drug: AM1476

Part B, Group 2: AM1476 375 mg BID (twice daily)

EXPERIMENTAL

Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state

Drug: AM1476

Part B, Group 3: AM1476 500 mg BID

EXPERIMENTAL

Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state

Drug: AM1476

Part B, Groups 1 to 3: Placebo

PLACEBO COMPARATOR

Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state

Drug: Placebo

Interventions

AM1476 DRUG

AM1476 Capsules

Part A, Group 1: AM1476 1 mg; Part A, Group 2: AM1476 5 mg; Part A, Group 3: AM1476 25 mg; Part A, Group 4: AM1476 125 mg; Part A, Group 5: AM1476 375 mg; Part A, Group 6: AM1476 650 mg; Part A, Group 7: AM1476 950 mg; Part A, Group 8: AM1476 1500 mg; Part A, Group 9: AM1476 2400 mg; Part B, Group 1: AM1476 100 mg QD (once daily); Part B, Group 2: AM1476 375 mg BID (twice daily); Part B, Group 3: AM1476 500 mg BID

Placebo DRUG

Placebo Capsules

Part A, Groups 1 to 9: Placebo; Part B, Groups 1 to 3: Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AnaMar AB: lead
• Covance: collaborator

Study Sites (1)

Covance Clinical Research Unit

Leeds, LS2 9LH, United Kingdom

Location

Results Point of Contact

• Title: Chief Medical Officer
• Organization: AnaMar AB

info@anamar.com

+46 (0)46-275 60 00

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A (SAD) Within each group, subjects will be randomised in a 3:1 ratio to receive either AM1476 (n=6) or placebo (n=2). 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. Part B (MAD) Within each group, subjects will be randomised in a 3:1 ratio to receive either AM1476 (n=6) or placebo (n=2).

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 31, 2020
• Study Start: December 16, 2020
• Primary Completion: December 8, 2021
• Study Completion: December 8, 2021
• Last Updated: August 2, 2024
• Results First Posted: August 2, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)