A Study of ORX489 in Healthy Adult Participants, Aged 18 to 60 Years

A Safety, Tolerability, Pharmacokinetic, Food Effect, and Proof-of-Concept Study of Single and Multiple Doses of ORX489 in Healthy Adults

Characterize the safety, tolerability and pharmacokinetics of ORX489 following single and multiple doses.

Study Overview

• Status: Recruiting
• Conditions: Healthy Adult Male and Female Volunteers
• Intervention / Treatment: Other: Placebo Tablets; Drug: ORX489 Tablets

• Study Type: Interventional
• Enrollment (Estimated): 212
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ORX489 Centessa Program Lead ORX489 Centessa Program Lead; Phone Number: 617-468-5770; Email: ORX489-101study@centessa.com
• Study Contact Backup: Name: Celerion Program Lead CA49982 United States, Nebraska [Recruiting]

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Recruiting
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy males or females as determined by assessments at the Screening Visit.
• For Parts A, B, C, and D: Participants must be at least 18 years of age and no more than 60 years of age at the Screening

Exclusion Criteria:

• 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.
• History of seizure disorder, any other condition that increases the risk of seizure
• Has a clinically significant sleep disorder, including insomnia or sleep apnea

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; SAD Study in Healthy Adults: ORX489 and Placebo	Other: Placebo Tablets; Placebo Tablets; Drug: ORX489 Tablets; ORX489 Tablets
Experimental: Part B; Food-effect Evaluation in Healthy Adults: ORX489	Drug: ORX489 Tablets; ORX489 Tablets
Experimental: Part C; MAD Study in Healthy Adults: ORX489 and Placebo	Other: Placebo Tablets; Placebo Tablets; Drug: ORX489 Tablets; ORX489 Tablets
Experimental: Part D; SAD Study in Acutely Sleep-Deprived Healthy Adults: ORX489 and Placebo	Other: Placebo Tablets; Placebo Tablets; Drug: ORX489 Tablets; ORX489 Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A	Incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability] as assessed by AEs and SAEs of oral single ascending doses of ORX489 in healthy adult participants.	From enrollment to the Follow-Up Visit 7 days post-discharge
Part B	Incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability] as assessed by AEs and SAEs of oral single ascending doses of ORX489 in the fasted and fed states	From enrollment to the Follow-Up Visit 7 days post-discharge]
Part C	Incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability] as assessed by AEs and SAEs of oral multiple ascending doses of ORX489 in healthy adult participants	From enrollment to the Follow-Up Visit 7 days post-discharge]
Part D:	Incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability] as assessed by AEs and SAEs of oral single oral doses of ORX489 in sleep-deprived healthy adult participants	From enrollment to the Follow-Up Visit 7 days post-discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum Observed Plasma Concentration for ORX489 in participants receiving ORX489	Pre-dose and multiple post-dose timepoints, up to 48 hours
Tmax	Time of Maximum Concentration for ORX489 in participants receiving ORX489	Pre-dose and multiple post-dose timepoints, up to 48 hours
AUClast	Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for ORX489 in participants receiving ORX489	Pre-dose and multiple post-dose timepoints, up to 48 hours
T 1/2 (terminal elimination half-life)	The time required for the terminal phase blood concentration of ORX489 to decrease by half in participants receiving ORX489	Pre-dose and multiple post-dose timepoints, up to 48 hours
Cmax	Maximum Observed Plasma Concentration for ORX489 in participants receiving ORX489 in the fasted and fed state.	Pre-dose and multiple post-dose timepoints, up to 48 hours
Tmax	Time of Maximum Concentration for ORX489 in participants receiving ORX489 in the fast and fed state	Pre-dose and multiple post-dose timepoints, up to 48 hours
AUClast	Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for ORX489 in participants receiving ORX489 in the fast and fed state	Pre-dose and multiple post-dose timepoints, up to 48 hours
T 1/2 (terminal elimination half-life)	The time required for the terminal phase blood concentration of ORX489 to decrease by half in participants receiving ORX489 in the fast and fed state	Pre-dose and multiple post-dose timepoints, up to 48 hours
Mean sleep latency in the Maintenance of Wakefulness Test (MWT)	Mean sleep latency in the Maintenance of Wakefulness Test (MWT) for ORX489 versus placebo: MWT sleep latency ranges from 0 to 40 minutes, with higher scores indicating greater ability to stay awake	Part D: Day 1-2
Karolinska Sleepiness Scale score	Karolinska Sleepiness Scale score for ORX489 versus placebo: 9-point scale, ranging from "extremely alert" (1) to "very sleepy, great effort keeping awake, fighting sleep	Part D: Day 1-2

Collaborators and Investigators

• Sponsor: Centessa Pharmaceuticals (UK) Limited

Study record dates

Study Major Dates

• Study Start (Estimated): February 25, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Healthy Volunteers orexin-2 receptor agonist
• Other Study ID Numbers: Protocol ORX489-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No