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A Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia

Phase 2
Recruiting
Conditions
Narcolepsy Type 1
Narcolepsy Type 2
Idiopathic Hypersomnia
Interventions
Drug: Placebo
Registration Number
NCT06752668
Lead Sponsor
Centessa Pharmaceuticals (UK) Limited
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. 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
78
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Narcolepsy Type 1: ORX750 and PlaceboORX750-
Narcolepsy Type 1: ORX750 and PlaceboPlacebo-
Narcolepsy Type 2: ORX750 and PlaceboPlacebo-
Idiopathic Hypersomnia: ORX750 and PlaceboPlacebo-
Idiopathic Hypersomnia: ORX750 and PlaceboORX750-
Narcolepsy Type 2: ORX750 and PlaceboORX750-
Primary Outcome Measures
NameTimeMethod
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEsUp to Day 49
Number of Participants With Abnormal Changes From Baseline in Laboratory TestsUp to Day 49
Number of Participants With Abnormal Change From Baseline in Vital SignsUp to Day 49
Number of Participants With Abnormal Change From Baseline in Electrocardiograms (ECG)Up to Day 49
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)Up to Day 49
Secondary Outcome Measures
NameTimeMethod
Cmax: Maximum Observed Plasma Concentration for ORX750Day 1
Tmax: Time of Maximum Concentration for ORX750Days 1, 14 and 28
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for ORX750Day 1
Cmax,ss: Maximum Observed Concentration at Steady State for ORX750Days 14 and 28
AUCτ: Area Under the Concentration-time Curve During a Dosing Interval at Steady State for ORX750Days 14 and 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 42

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 41

Trial Locations

Locations (18)

Newton, Massachusetts

🇺🇸

Newton, Massachusetts, United States

Scottsdale, Arizona

🇺🇸

Scottsdale, Arizona, United States

Long Beach, California

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Long Beach, California, United States

Santa Ana, California

🇺🇸

Santa Ana, California, United States

Sterling Heights, Michigan

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Sterling Heights, Michigan, United States

North Charleston, South Carolina

🇺🇸

North Charleston, South Carolina, United States

Austin, Texas

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Austin, Texas, United States

Chandler, Arizona

🇺🇸

Chandler, Arizona, United States

Miami, Florida

🇺🇸

Miami, Florida, United States

Winter Park, Florida

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Winter Park, Florida, United States

Atlanta, Georgia

🇺🇸

Atlanta, Georgia, United States

Henderson, Nevada

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Henderson, Nevada, United States

Denver, North Carolina

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Denver, North Carolina, United States

Huntersville, North Carolina

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Huntersville, North Carolina, United States

Cincinnati, Ohio

🇺🇸

Cincinnati, Ohio, United States

Columbia, South Carolina

🇺🇸

Columbia, South Carolina, United States

San Antonio, Texas

🇺🇸

San Antonio, Texas, United States

Toronto, Ontario

🇨🇦

Toronto, Ontario, Canada

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