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
- Are there results?
- Not yet: the study is under way
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
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety, Tolerability, Pharmacokinetic, Food Effect, and Proof-of-Concept Study of Single and Multiple Doses of ORX489 in Healthy Adults
- ClinicalTrials.gov ID
- NCT07413666
- Acronym / sponsor ID
- Protocol ORX489-101
- Conditions
- Healthy Adult Male and Female Volunteers
- Keywords
- Healthy Volunteers orexin-2 receptor agonist
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 212 participants (estimated)
- Lead sponsor
- Centessa Pharmaceuticals (UK) LimitedIndustry (pharma, biotech, devices)
- Study start
- 25 Feb 2026 (estimated)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 17 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Characterize the safety, tolerability and pharmacokinetics of ORX489 following single and multiple doses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A | Experimental | Drug: ORX489 Tablets, Other: Placebo TabletsSAD Study in Healthy Adults: ORX489 and Placebo |
| Part B | Experimental | Drug: ORX489 TabletsFood-effect Evaluation in Healthy Adults: ORX489 |
| Part C | Experimental | Drug: ORX489 Tablets, Other: Placebo TabletsMAD Study in Healthy Adults: ORX489 and Placebo |
| Part D | Experimental | Drug: ORX489 Tablets, Other: Placebo TabletsSAD Study in Acutely Sleep-Deprived Healthy Adults: ORX489 and Placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ORX489 TabletsORX489 Tablets | Drug | Part A, Part B, Part C, Part D |
| Placebo TabletsPlacebo Tablets | Other | Part A, Part C, Part D |
Primary outcome
Part A
Time frame: From enrollment to the Follow-Up Visit 7 days post-discharge
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.
Part B
Time frame: From enrollment to the Follow-Up Visit 7 days post-discharge]
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
Part C
Time frame: From enrollment to the Follow-Up Visit 7 days post-discharge]
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
Part D:
Time frame: From enrollment to the Follow-Up Visit 7 days post-discharge
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
10 secondary outcomes
Cmax
Time frame: Pre-dose and multiple post-dose timepoints, up to 48 hours
Tmax
Time frame: Pre-dose and multiple post-dose timepoints, up to 48 hours
AUClast
Time frame: Pre-dose and multiple post-dose timepoints, up to 48 hours
T 1/2 (terminal elimination half-life)
Time frame: Pre-dose and multiple post-dose timepoints, up to 48 hours
Cmax
Time frame: Pre-dose and multiple post-dose timepoints, up to 48 hours
Tmax
Time frame: Pre-dose and multiple post-dose timepoints, up to 48 hours
AUClast
Time frame: Pre-dose and multiple post-dose timepoints, up to 48 hours
T 1/2 (terminal elimination half-life)
Time frame: Pre-dose and multiple post-dose timepoints, up to 48 hours
Mean sleep latency in the Maintenance of Wakefulness Test (MWT)
Time frame: Part D: Day 1-2
Karolinska Sleepiness Scale score
Time frame: Part D: Day 1-2
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
ORX489 Centessa Program Lead ORX489 Centessa Program Lead contact
Celerion Program Lead CA49982 United States, Nebraska [Recruiting] contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact ORX489 Centessa Program Lead ORX489 Centessa Program Lead (617-468-5770, ORX489-101study@centessa.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A (time frame: From enrollment to the Follow-Up Visit 7 days post-discharge). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2026.