Clinical trial NCT03869320: A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of ACT-1004-1239 in Healthy Male Subjects
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2019-03-11
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: OTHER

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.


Eligibility 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.

Primary outcomes:
measure: Number of patients with treatment-emergent (serious) adverse events (AEs and SAEs)
timeFrame: From baseline up to EOS of each cohort (total duration: up to 6 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Pharmaron CPC, Inc. & Affiliates
state: Maryland
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.