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NCT Number: NCT06752668

A Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia

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.

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Toronto, Ontario, Toronto, Ontario, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ORX750

Drug

ORX750 capsule.

Placebo

Drug

ORX750 matching placebo capsule.

Primary outcomes

  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

    Time frame: Up to Day 35

  2. Number of Participants With Abnormal Changes From Baseline in Laboratory Tests

    Time frame: Up to Day 35

  3. Number of Participants With Abnormal Change From Baseline in Vital Signs

    Time frame: Up to Day 35

  4. Number of Participants With Abnormal Change From Baseline in Electrocardiograms (ECG)

    Time frame: Up to Day 35

  5. Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)

    Time frame: Up to Day 35

Secondary outcomes

  1. Cmax: Maximum Observed Plasma Concentration for ORX750

    Time frame: Day 1, 15, 28

  2. Tmax: Time of Maximum Concentration for ORX750

    Time frame: Day 1, 15, 28

  3. AUC0last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for ORX750

    Time frame: up to Day 28

  4. Cmax,ss: Maximum Observed Concentration at Steady State for ORX750

    Time frame: Day 1, 15, 28

  5. AUCτ: Area Under the Concentration-time Curve During a Dosing Interval at Steady State for ORX750

    Time frame: Day 1, 15, 28

  6. Mean sleep latency (average of the first 4 trials) in the Maintenance of Wakefulness Test (MWT) for ORX750 versus placebo.

    Time frame: Baseline up to Day 28

    Mean sleep latency is determined by averaging the time to falling asleep across trials

  7. Change From Baseline in Epworth Sleepiness Scale (ESS)

    Time frame: Baseline up to Day 28

Study contacts

Contact information is provided by the study sponsor or research team.

Centessa Pharmaceuticals

CONTACT

[email protected]

+1 617-468-5770

Sponsors and collaborators

Lead sponsor

Centessa Pharmaceuticals (UK) Limited

Industry

Registry information

Official study title

A Phase 2a, Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ORX750 in Subjects With Narcolepsy and Idiopathic Hypersomnia (CRYSTAL-1)

Acronym: CRYSTAL-1

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Dec 31, 2024
Registry last updated
Apr 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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