ACT-1014-6470 / Idorsia - LARVOL DELTA

Modeling time-delayed concentration-QT effects with ACT-1014-6470, a novel oral complement factor 5a receptor 1 (C5a receptor) antagonist. (PubMed, Pharmacol Res Perspect) - "doses of 10 mg did not exceed the regulatory threshold of 10 ms but would achieve ACT-1014-6470 plasma concentrations enabling adequate target engagement. Results from cardiodynamic assessments identified dose levels and dosing regimens that could be considered for future clinical trials, attempting to reduce QT liability."

Journal

Evaluation of the cytochrome P450 2C19 and 3A4 inhibition potential of the complement factor 5a receptor antagonist ACT-1014-6470 in vitro and in vivo. (PubMed, Clin Transl Sci) - "In humans, GMRs (90% CI) of omeprazole PK were 1.9 (1.5-2.5) for maximum plasma concentration (C ) and 1.9 (1.5-2.3) for area under the plasma concentration-time curve (AUC) from 0 to 12 h. Midazolam PK showed GMRs (90% CI) of 1.1 (1.1-1.2) for C and 1.5 (1.4-1.6) for AUC from 0 to 24 h. All treatments were well tolerated. In line with in vitro results and regulatory risk factor calculation, the increased exposure to omeprazole and midazolam in humans after concomitant administration with a single dose of 100 mg ACT-1014-6470 reflected a weak inhibition of CYP2C19 and CYP3A4."

Journal • Preclinical • Inflammation • CYP2C19 • CYP3A4

Effect of Severe Renal Impairment on Pharmacokinetics, Safety, and Tolerability of ACT-1014-6470, a Novel Oral Complement Factor 5a Receptor 1 Antagonist. (PubMed, Clin Pharmacol Drug Dev) - "Four transient and mild AEs in three subjects with severe RI were reported; three AEs were considered not related to ACT-1014-6470. These results support the use of ACT-1014-6470 in subjects with mild to severe RI without the need of dose adjustment."

Journal • PK/PD data • Hematological Disorders • Renal Disease

Multiple-ascending doses of ACT-1014-6470, an oral complement factor 5a receptor 1 (C5a receptor) antagonist: tolerability, pharmacokinetics, and target engagement. (PubMed, Br J Clin Pharmacol) - "The compound was generally safe and well tolerated at all dose levels, warranting further clinical investigations."

Journal • PK/PD data • Immunology • MMP9

First-in-human study with ACT-1014-6470, a novel oral complement factor 5a receptor 1 (C5aR1) antagonist, supported by pharmacokinetic predictions from animals to patients. (PubMed, Basic Clin Pharmacol Toxicol) - "No clinically relevant findings were observed in safety assessments. ACT-1014-6470 was well tolerated at all doses and could provide a novel therapy with more patient-friendly administration route compared to biologicals."

Clinical • Journal • P1 data • PK/PD data • Inflammation

Pharmacokinetics of Omeprazole and Midazolam When Co-administered With ACT-1014-6470 (clinicaltrials.gov) - P1; N=20; Completed; Sponsor: Idorsia Pharmaceuticals Ltd.; Recruiting ➔ Completed

Clinical • Trial completion

Pharmacokinetics of Omeprazole and Midazolam When Co-administered With ACT-1014-6470 (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study to Investigate the Pharmacokinetics of ACT-1014-6470 in Subjects With Severe Renal Impairment Compared to Control Subjects (clinicaltrials.gov) - P1; N=16; Completed; Sponsor: Idorsia Pharmaceuticals Ltd.; Not yet recruiting ➔ Completed

Clinical • Trial completion • Renal Disease

Study to Evaluate the Effect of Co-administered ACT-1014-6470 on the Pharmacokinetics of Omeprazole and Midazolam (clinicaltrials.gov) - P1; N=20; Not yet recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.

Clinical • New P1 trial

A Placebo-controlled Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-1014-6470 in Healthy Subjects (clinicaltrials.gov) - P1; N=46; Completed; Sponsor: Idorsia Pharmaceuticals Ltd.; Recruiting ➔ Completed

Clinical • Trial completion

A Study to Investigate the Pharmacokinetics of ACT-1014-6470 in Subjects With Severe Renal Impairment Compared to Control Subjects (clinicaltrials.gov) - P1; N=16; Not yet recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.

Clinical • New P1 trial • Renal Disease

A Placebo-controlled Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-1014-6470 in Healthy Subjects (clinicaltrials.gov) - P1; N=56; Recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Placebo-controlled Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-1014-6470 in Healthy Subjects (clinicaltrials.gov) - P1; N=56; Not yet recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.

Clinical • New P1 trial

A Study to Examine the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-1014-6470 in Healthy Subjects (clinicaltrials.gov) - P1; N=88; Completed; Sponsor: Idorsia Pharmaceuticals Ltd.; Active, not recruiting ➔ Completed; Trial completion date: Jul 2020 ➔ Mar 2020; Trial primary completion date: Jul 2020 ➔ Mar 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date

A Study to Examine the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-1014-6470 in Healthy Subjects (clinicaltrials.gov) - P1; N=88; Active, not recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.; Not yet recruiting ➔ Active, not recruiting

Clinical • Enrollment closed