Idiopathic Hypersomnia, Narcolepsy Type 1, Narcolepsy Type 2
Conditions
Brief summary
Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2), and Idiopathic Hypersomnia (IH) are rare conditions that make people feel very sleepy during the day (often referred to as excessive daytime sleepiness \[EDS\]). People living with these conditions might find it hard to stay alert and pay attention when they are at school, working, driving, or performing other daily activities. While all conditions result in feeling sleepy, there are some differences in other common symptoms: * NT1: People with NT1 often feel very tired during the day and experience cataplexy. Cataplexy is a sudden loss of muscle strength, which can cause someone to collapse or lose control of their muscles for a short time. This is often triggered by strong emotions, such as laughter or surprise. They may also have trouble sleeping well at night. * NT2: People with NT2 feel sleepy during the day, just like NT1, but they do not have cataplexy. * IH: People with IH feel tired during the day, even after sleeping a lot at night. They may sleep for long periods, take long naps, and find it hard to wake up. Orexin is a protein in the brain that helps coordinate a system that plays an important role in helping people to stay awake during the daytime. Cleminorexton (also known as ORX750) is designed to mimic the action of orexin. The purpose of this study is to see how safe and tolerable ORX750 is in NT1, NT2, and IH, and learn about what the drug does to the body. Another goal of the study is to see if ORX750 can help people with NT1, NT2, and IH feel less sleepy and make other symptoms better.
Interventions
DRUGORX750
ORX750 capsule.
DRUGPlacebo
ORX750 matching placebo capsule.
Sponsors
Centessa Pharmaceuticals (UK) Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18-65 years of age * BMI ≥17 and ≤37 kg/m2 * Meets the diagnostic criteria of Narcolepsy Type 1 (NT1), Type 2 (NT2) or Idiopathic Hypersomnia (IH) according to ICSD-3-TR criteria * Is willing and able to discontinue all medications used for the treatment of narcolepsy or idiopathic hypersomnia * Is willing and able to adhere to additional protocol requirements
Exclusion criteria
* A medical disorder other than NT1, NT2, or IH that is associated with excessive daytime sleepiness (EDS). * Presence of significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, hematological, malignancy, endocrine, neurological or psychiatric disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Up to Day 35 |
| Number of Participants With Abnormal Changes From Baseline in Laboratory Tests | Up to Day 35 |
| Number of Participants With Abnormal Change From Baseline in Vital Signs | Up to Day 35 |
| Number of Participants With Abnormal Change From Baseline in Electrocardiograms (ECG) | Up to Day 35 |
| Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) | Up to Day 35 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for ORX750 | Day 1, 15, 28 | — |
| Tmax: Time of Maximum Concentration for ORX750 | Day 1, 15, 28 | — |
| AUC0last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for ORX750 | up to Day 28 | — |
| Cmax,ss: Maximum Observed Concentration at Steady State for ORX750 | Day 1, 15, 28 | — |
| AUCτ: Area Under the Concentration-time Curve During a Dosing Interval at Steady State for ORX750 | Day 1, 15, 28 | — |
| Mean sleep latency (average of the first 4 trials) in the Maintenance of Wakefulness Test (MWT) for ORX750 versus placebo. | Baseline up to Day 28 | Mean sleep latency is determined by averaging the time to falling asleep across trials |
| Change From Baseline in Epworth Sleepiness Scale (ESS) | Baseline up to Day 28 | — |
Countries
Canada, France, Italy, Spain, United States
Contacts
CONTACTCentessa Pharmaceuticals
Outcome results
None listed