Narcolepsy Type 1, Narcolepsy Type 2
Conditions
Keywords
NT1, NT2, Excessive Daytime Sleepiness, Orexin Receptor 2 agonist, Central Disorders of Hypersomnia, Disorders of Excessive Somnolence, Dyssomnias, Nervous System Diseases, Mental Disorders, Hypersomnia, Hypersomnolence, Sleep Wake Disorders, Sleep Disorder, Sleep, Sleepiness, Cataplexy, Narcolepsy Type 1, Narcolepsy Type 2, Orexin, ORX750, Cleminorexton, Narcolepsy, SAPPHIRE
Brief summary
Narcolepsy Type 1 (NT1) and Narcolepsy Type 2 (NT2) 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. 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 is designed to mimic the action of orexin. The purpose of this study is to see how safe and tolerable cleminorexton is in NT1 and NT2 and learn about what the drug does to the body. Another goal of the study is to see if cleminorexton can help people with NT1 and NT2 feel less sleepy and make other symptoms better.
Detailed description
The SAPPHIRE Clinical Trial The Sponsor may in the future, through a protocol amendment, expand the protocol to include participants with idiopathic hypersomnia (IH) in Cohort C.
Interventions
DRUGcleminorexton
Oral cleminorexton capsule
DRUGPlacebo
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 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 18-70 years of age * Body Mass Index (BMI) within the range ≥ 17.0 and ≤ 45 kg/m\^2 (inclusive) * Meets the diagnostic criteria of Narcolepsy Type 1 (NT1) or Type 2 (NT2) according to International Classification of Sleep Disorders, 3rd edition, Text Revision edition (ICSD-3-TR) criteria * Is willing and able to discontinue all medications used for the treatment of narcolepsy * Is willing and able to adhere to additional protocol requirements Key
Exclusion criteria
* Medical disorder other than NT1 or NT2, 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 |
|---|---|
| Change from baseline in mean sleep latency (average of the first 4 trials) on the Maintenance of Wakefulness Test (MWT) | Baseline to week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in Epworth Sleepiness Scale (ESS) total score | Baseline to Week 12 | — |
| Weekly Cataplexy Rate (WCR) | Week 12 | Measurement specific to Group A |
| Change from baseline in Narcolepsy Severity Scale for Clinical Trials (NSS-CT) | Baseline to Week 12 | Measurement specific to Group A |
| Change from baseline in Narcolepsy Severity Scale-2 for Clinical Trials (NSS2-CT) total score | Baseline to Week 12 | Measurement specific to Group B |
| Incidence, Severity, and casual relationship of participants with Treatment Emergent Adverse Events (TEAEs) | Baseline to Week 12 | — |
| Number of participants with abnormal changes from baseline in clinical laboratory tests | Baseline to Week 12 | — |
| Number of participants with abnormal changes from baseline in vital signs | Baseline to Week 12 | — |
| Number of participants with abnormal changes from baseline in 12-lead electrocardiograms (ECGs) | Baseline to Week 12 | — |
| Number of participants with at least 1 endorsement of Item 4 or 5 on Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline to Week 12 | — |
| Cmax: Maximum observed plasma concentration | Baseline to Week 12 | — |
| Tmax: Time of Maximum Concentration for cleminorexton | Baseline to Week 12 | — |
| AUC: Area under the plasma concentration-time curve | Baseline to Week 12 | — |
Countries
United States
Contacts
CONTACTCentessa Pharmaceuticals
Outcome results
None listed