A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of ACT-1004-1239 in Healthy Male Subjects

NCT03869320 | Completed Phase 1 FDA Drug

• 1 other identifier: ID-086-101
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 1 study will assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of ACT-1004-1239 in healthy subjects.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Number of patients with treatment-emergent (serious) adverse events (AEs and SAEs)

  From baseline up to EOS of each cohort (total duration: up to 6 weeks)

Study Arms (4)

ACT-1004-1239

EXPERIMENTAL

ACT-1004-1239 will be given as a single oral dose under fasting conditions. Eight doses are planned with a starting dose of 1 mg. The ADME characteristics and absolute bioavailability using a 14C-radiolabeled microtracer will be evaluated as part of the SAD, after the first 3 cohorts have been performed.

Drug: ACT-1004-1239

Placebo

PLACEBO COMPARATOR

Matching placebo will be given as a single oral dose under fasted conditions. Matching placebo for the oral and intravenous administration of the 14C-radiolabeled ACT-1004-1239 will also be available.

Other: Placebo

Food-effect subpart: ACT-1004-1239

EXPERIMENTAL

ACT-1004-1239 will be given under both fasted (first period) and fed (second period) conditions. The food effect will be evaluated after the first 3 cohorts have been performed.

Drug: ACT-1004-1239 (Food-effect subpart)

Food-effect subpart: Placebo

PLACEBO COMPARATOR

Matching placebo will be given under both fasted (first period) and fed (second period) conditions.

Other: Placebo (Food-effect subpart)

Interventions

ACT-1004-1239 DRUG

ACT-1004-1239 will be available for clinical study use as hard gelatin capsules for oral administration formulated in strengths of 1, 10, and 100 mg. For the ADME subpart, a single oral dose of 1 μCi of 14C radiolabeled ACT-1004-1239 will be given simultaneously with the ACT-1004-1239 capsule. For the absolute bioavailability subpart, a single intravenous dose of a maximum of 1 μCi of 14C radiolabeled ACT-1004-1239 will be given at the expected tmax after the administration of the ACT-1004-1239 capsule.

ACT-1004-1239

Placebo OTHER

Matching placebo is available as matching capsules for oral administration, formulated with the same excipients but without ACT-1004-1239.

Placebo

ACT-1004-1239 (Food-effect subpart) DRUG

ACT-1004-1239 will be available for clinical study use as hard gelatin capsules for oral administration formulated in strengths of 1, 10, and 100 mg.

Food-effect subpart: ACT-1004-1239

Placebo (Food-effect subpart) OTHER

Matching placebo is available as matching capsules for oral administration, formulated with the same excipients but without ACT-1004-1239.

Food-effect subpart: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.
• Healthy male subjects aged between 18 and 55 years (inclusive) at Screening.
• No sperm donation from (first) study treatment administration up to at least 90 days after (last) study treatment administration.
• Sexual abstinence or use of condoms from (first) treatment administration up to at least 90 days after (last) study treatment administration. Moreover, the female partner of childbearing potential must use a highly effective method of contraception.

You may not qualify if:

• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• Any previous and/or ongoing relevant immune-related disorder or any evidence for immune dysfunction based on medical history and laboratory tests at Screening
• Any cardiac condition or illness (including clinically relevant 12-lead ECG abnormalities) with a potential to increase the cardiac risk of the subject based on medical history and 12-lead ECG measured at Screening.
• QT interval corrected with Fridericia's formula (QTcF) \> 430 ms, respectively, QRS interval \> 110 ms, PR interval \> 200 ms, or heart rate (HR) \> 90 bpm on 12-lead ECG at Screening and Day 1 pre-dose (of the first period when applicable).
• Treatment with another investigational treatment within the 2 months prior to Screening or participation in more than 3 investigational treatment studies within the year prior to Screening.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition that might interfere with the ADME of the study treatment (e.g., appendectomy and herniotomy allowed, cholecystectomy not allowed).
• Previous treatment with any prescribed medications (including vaccines and strong CYP3A4 inhibitors/inducers) or over-the-counter (OTC) medications (including homeopathic preparations, herbal medicines, vitamins, and minerals) within the 2 weeks or 5 terminal half-lives (t½; whichever is longer) prior to (first) study treatment administration.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

Pharmaron CPC, Inc. & Affiliates

Baltimore, Maryland, 21201, United States

Location

Related Publications (2)

• Huynh C, Seeland S, Segrestaa J, Gnerre C, Hogeback J, Meyer Zu Schwabedissen HE, Dingemanse J, Sidharta PN. Absorption, Metabolism, and Excretion of ACT-1004-1239, a First-In-Class CXCR7 Antagonist: In Vitro, Preclinical, and Clinical Data. Front Pharmacol. 2022 Mar 30;13:812065. doi: 10.3389/fphar.2022.812065. eCollection 2022.

  PMID: 35431953 DERIVED

• Pouzol L, Baumlin N, Sassi A, Tunis M, Marrie J, Vezzali E, Farine H, Mentzel U, Martinic MM. ACT-1004-1239, a first-in-class CXCR7 antagonist with both immunomodulatory and promyelinating effects for the treatment of inflammatory demyelinating diseases. FASEB J. 2021 Mar;35(3):e21431. doi: 10.1096/fj.202002465R.

  PMID: 33595155 DERIVED

MeSH Terms

Interventions

ACT-1004-1239

Study Officials

• Clinical Trials

  Idorsia Pharmaceuticals Ltd.

  STUDY DIRECTOR

Study Design

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

Model Details: Single-center, double-blind, randomized, placebo-controlled, single-ascending dose, Phase 1 study. The food effect will be assessed using a two-period, fixed-sequence design.

Study Record Dates

• First Submitted: March 8, 2019
• First Posted: March 11, 2019
• Study Start: March 25, 2019
• Primary Completion: July 11, 2019
• Study Completion: July 11, 2019
• Last Updated: January 10, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)