ORX142 in healthy adults aged 18–80

A Randomized, Double-blind, Sponsor-open, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Food Effect of Single and Multiple Ascending Doses of ORX142 in Healthy Adults, Single Doses of ORX142 in Healthy Older Adults, and a Single Dose Crossover, Proof-of-concept Study of ORX142 in Acutely Sleep-deprived Healthy Subjects

This trial tests ORX142, an orexin-2 receptor agonist, to see if it is safe, well tolerated, and how the body processes it in healthy adults aged 18–80.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 208 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Centessa Pharmaceuticals (UK) Limited (Industry-sponsored)
• Locations: 3 sites (Lincoln, Nebraska and 2 other locations)
• Trial ID: NCT07082829 on ClinicalTrials.gov

What this trial studies

This Phase 1 study gives single and multiple oral doses of ORX142 or matching placebo to healthy adult volunteers to characterize safety, tolerability, and pharmacokinetics. Most study parts enroll adults 18–55, with a separate older cohort enrolling ages 60–80 in Part D. Participants are screened to exclude significant medical or sleep disorders and seizure risk, and will undergo clinical assessments, safety monitoring, and blood sampling for drug levels. The study is conducted at three U.S. sites in Nebraska, New Jersey, and New York.

Who should consider this trial

Good fit: Ideal candidates are healthy adults within the study age windows (18–55 for most parts, 60–80 for the older cohort) with no significant medical conditions, no clinically significant sleep disorders, and no history of seizures.

Not a fit: People with significant cardiac, pulmonary, hepatic, renal, neurological, or psychiatric disease, a history of seizures, or clinically significant sleep disorders such as insomnia or sleep apnea are unlikely to be eligible or to benefit from participation.

Why it matters

Potential benefit: If successful, ORX142 could provide a new treatment option to reduce excessive daytime sleepiness by activating orexin-2 receptors.

How similar studies have performed: Early clinical work with other orexin-2 receptor agonists has shown wake-promoting effects in small studies, but clinical experience remains limited.

Eligibility criteria

Key Inclusion Criteria:

1. Healthy males or females as determined by assessments at the Screening Visit.

   For Parts A, B, C, and E:

   a. Participants must be at least 18 years of age and no more than 55 years of age at the Screening
2. For Part D:

a .Participants must be at least 60 years of age and no more than 80 years of age at the Screening

Key Exclusion Criteria:

1. Presence of significant cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, malignancy, endocrine, neurological, or psychiatric disease, as determined by medical history, physical examination, and screening investigations.
2. History of seizure disorder, any other condition that increases the risk of seizure
3. Has a clinically significant sleep disorder, including insomnia or sleep apnea.

Where this trial is running

Lincoln, Nebraska and 2 other locations

• Site #1 — Lincoln, Nebraska, United States (Recruiting)
• Site #2 — Eatontown, New Jersey, United States (Recruiting)
• Site #3 — New York, New York, United States (Recruiting)

Study contacts

• Study coordinator: ORX142 Centessa Program Lead

Conditions Excessive Daytime Sleepiness; orexin-2 receptor agonist