Healthy Adult Male and Female VolunteersPhase 1NCT07413666
A Study of ORX489 in Healthy Adult Participants, Aged 18 to 60 Years
A Phase 1 study testing ORX489 Tablets in people with Healthy Adult Male and Female Volunteers, run by Centessa Pharmaceuticals (UK) Limited at 1 site in United States.
Trial summary
Characterize the safety, tolerability and pharmacokinetics of ORX489 following single and multiple doses. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Adult Male and Female Volunteers
- What is being tested?
- ORX489 Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 212 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2026to 30 Jun 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
ORX489 Centessa Program Lead ORX489 Centessa Program Lead contact
Celerion Program Lead CA49982 United States, Nebraska [Recruiting] contact
United States1 site, 1 recruiting
- Recruiting
Celerion
Lincoln, Nebraska, 68502
About this study
Official title: 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.
- Conditions
- Healthy Adult Male and Female Volunteers
- Being tested
- ORX489 Tablets, Placebo Tablets
- Keywords
- Healthy Volunteers orexin-2 receptor agonist
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ORX489 TabletsDrug
ORX489 Tablets
Placebo TabletsOther
Placebo Tablets
| Study group | Role | What they receive |
|---|---|---|
| Part A | Experimental | SAD Study in Healthy Adults: ORX489 and Placebo Receives: Drug: ORX489 Tablets; Other: Placebo Tablets |
| Part B | Experimental | Food-effect Evaluation in Healthy Adults: ORX489 Receives: Drug: ORX489 Tablets |
| Part C | Experimental | MAD Study in Healthy Adults: ORX489 and Placebo Receives: Drug: ORX489 Tablets; Other: Placebo Tablets |
| Part D | Experimental | SAD Study in Acutely Sleep-Deprived Healthy Adults: ORX489 and Placebo Receives: Drug: ORX489 Tablets; Other: Placebo Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 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
Measured: From enrollment to the Follow-Up Visit 7 days post-discharge
Secondary outcomes (10)
Cmax
Maximum Observed Plasma Concentration for ORX489 in participants receiving ORX489
Measured: Pre-dose and multiple post-dose timepoints, up to 48 hours
Tmax
Time of Maximum Concentration for ORX489 in participants receiving ORX489
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Part D: Day 1-2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2026
- Study start25 Feb 2026 (estimated)
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy Adult Male and Female VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 212 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centessa Pharmaceuticals (UK) Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07413666
- Sponsor's protocol ID
- Protocol ORX489-101
- Status last verified
- Feb 2026
- First submitted
- 9 Feb 2026
- Last updated
- 25 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No