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

• ClinicalTrials.gov Identifier: NCT03869320
• Recruitment Status: Completed
• First Posted: March 11, 2019
• Last Update Posted: January 10, 2020
• Sponsor: Idorsia Pharmaceuticals Ltd.
• Information provided by (Responsible Party): Idorsia Pharmaceuticals Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: ACT-1004-1239; Other: Placebo; Drug: ACT-1004-1239 (Food-effect subpart); Other: Placebo (Food-effect subpart)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 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.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: A Single-center, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of ACT-1004-1239 in Healthy Male Subjects (Including Food Interaction, Absolute Bioavailability, Mass Balance, and Metabolite Profiling)
• Actual Study Start Date: March 25, 2019
• Actual Primary Completion Date: July 11, 2019
• Actual Study Completion Date: July 11, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: ACT-1004-1239; 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; 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.
Placebo Comparator: Placebo; 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; Matching placebo is available as matching capsules for oral administration, formulated with the same excipients but without ACT-1004-1239.
Experimental: Food-effect subpart: ACT-1004-1239; 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); 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.
Placebo Comparator: Food-effect subpart: Placebo; Matching placebo will be given under both fasted (first period) and fed (second period) conditions.	Other: Placebo (Food-effect subpart); Matching placebo is available as matching capsules for oral administration, formulated with the same excipients but without ACT-1004-1239.

Outcome Measures

Primary Outcome Measures :

1. Number of patients with treatment-emergent (serious) adverse events (AEs and SAEs) [ Time Frame: From baseline up to EOS of each cohort (total duration: up to 6 weeks) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Contacts and Locations

Locations

United States, Maryland

Pharmaron CPC, Inc. & Affiliates

Baltimore, Maryland, United States, 21201

Sponsors and Collaborators

Idorsia Pharmaceuticals Ltd.

Investigators

• Study Director: Clinical Trials; Idorsia Pharmaceuticals Ltd.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Idorsia Pharmaceuticals Ltd.
• ClinicalTrials.gov Identifier: NCT03869320
• Other Study ID Numbers: ID-086-101
• First Posted: March 11, 2019
• Last Update Posted: January 10, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No