E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Narcolepsy without Cataplexy (Type 2) |
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E.1.1.1 | Medical condition in easily understood language |
Narcolepsy without Cataplexy (Type 2) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028713 |
E.1.2 | Term | Narcolepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of TAK-861 on EDS as measured by sleep latency from the MWT |
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E.2.2 | Secondary objectives of the trial |
- To assess the effect of TAK-861 on EDS as measured by the Epworth Sleepiness Scale (ESS) total score. - To evaluate the safety and tolerability of TAK-861
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The participant is willing and able to understand and fully comply with study procedures and requirements (including digital tools and applications), in the opinion of the investigator. 2. The participant has provided informed consent (that is, in writing, documented via a signed and dated informed consent form [ICF] and/or electronic consent) and any required privacy authorization before the initiation of any study procedures Age and Body Mass Index 1. The participant is aged 18 to 70 years, inclusive, at the time of signing the ICF. Note: In Japan, participants aged 16 to 70 years, inclusive, may be included. 2. The participant has body mass index within the range 18 to 40 kg/m2 (inclusive) Type of Participant and Disease Characteristics 1. The participant has an ICSD-3 diagnosis of NT2 by PSG/MSLT, performed within the past 5 years and meeting the minimal acceptable criteria for the proper performance of PSG/MSLT as outlined in the ICSD-3. Note: If there is a potential participant with NT2 for whom a diagnostic nPSG/MSLT was performed more than 5 years ago or is not available, the site may repeat the diagnostic PSG/MSLT before Day -2. 2. The participant has an ESS score >12 on Day -1. 3. The participant is judged by the investigator to be sufficiently healthy to participate in the study, on the basis of clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead ECG, and vital sign measurements performed at the screening visit and before the first dose of study drug. Note: Screening laboratory assessments may be repeated; the sponsor or designee should be informed. Contraception 1. The participant agrees to follow the birth control requirements
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E.4 | Principal exclusion criteria |
Medical Conditions 1. The participant has a current medical disorder, other than narcolepsy without cataplexy, associated with EDS a. Restless legs syndrome/periodic limb movement disorder that has a significant impact on daytime sleepiness b. Clinically significant moderate-to-severe obstructive sleep apnea (with or without treatment) or obstructive sleep apnea of any severity treated with positive airway pressure or oral appliance. c. Past PSG data demonstrating any of the following: apnea hypopnea index ≥15, apnea index ≥10, or periodic leg movement arousal index of ≥15/hour, unless a more recent PSG and/or clinical evaluation by the investigator indicates a meaningful change in clinical status. All attempts should be made to confirm eligibility based on Day -2 nPSG data 2. The participant has a current medical condition such as unstable cardiovascular, pulmonary, renal, or gastrointestinal disease, that would preclude enrollment in the view of the investigator 3. The participant has medically significant hepatic or thyroid disease. 4. The participant has current or recent (within 6 months) gastrointestinal disease that is expected to influence the absorption of drugs. Any history of Roux-en-Y gastric bypass is considered exclusionary, and any other surgical intervention that may influence the absorption of drugs should be discussed and approved by the sponsor or designee before enrolling the participant 5. The participant has a history of cancer in the past 5 years (does not apply to participants with carcinoma in situ that has been resolved without further treatment or basal cell cancer; these participants may be included after approval by the sponsor or designee) 6. The participant has clinically significant coronary artery disease, a history of myocardial infarction, clinically significant angina, clinically significant cardiac rhythm abnormality, or heart failure 7. The participant has a clinically significant history of head injury or head trauma 8. The participant has a history of epilepsy, seizure, or convulsion, or has a family history of inherited disorders associated with seizure (except for a single febrile seizure in childhood) 9. The participant has one or more of the following psychiatric disorders: a. Any current unstable psychiatric disorder. b. Current or history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including schizoaffective disorder, major depression with psychotic features, bipolar depression with psychotic features, obsessive compulsive disorder, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the (DSM-5) c. Current diagnosis or history of substance use disorder as defined in the DSM-5. d. Current active (MDE) or who have had an active MDE in the past 6 months. 10. The participant has a history of cerebral ischemia, transient ischemic attack (<5 years ago), intracranial aneurysm, or arteriovenous malformation. 11. The participant has a current history of significant multiple or severe allergies or has had an anaphylactic reaction or significant intolerance to prescription or nonprescription drugs or food 12. The participant has a known hypersensitivity to any component of the formulation of TAK-861 or related compounds. 13. The participant had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks before the screening visit 14. The participant is unable to refrain from or anticipates using excluded food products, beginning by Day -7 and continuing until the first follow-up visit, or prohibited medication 15. The participant has participated in another investigational drug study, in which they received the investigational drug, within 60 days (or 6 months if participant may have received an investigational biologic product). The interval window from the previous study will be derived from the date of the last study procedure in the previous study to the screening visit of the current study 16. The participant has any prior exposure to an oral Takeda OX2R agonist other than TAK-861 17. The participant has a BP >140 mm Hg (systolic) or >90 mm Hg (diastolic) during screening. BP measures should be obtained after the participant has been resting for a minimum of 5 minutes. If the BP is slightly elevated above these parameters, measurement may be repeated 3 times, and the median of the 3 recordings used. 18. The participant has a resting HR <40 or >100 beats per minute during screening, confirmed on repeat testing within a maximum of 30 minutes 19. The participant’s screening ECG reveals a QT interval with Fridericia correction method >450 milliseconds (genetically male) or >470 milliseconds (genetically female)
For further exclusion criteria number 20-42 please refer to the study protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to Week 8 in mean sleep latency from the MWT |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change from baseline to Week 8 in ESS total score - Occurrence of at least 1 treatment-emergent adverse event (TEAE)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Japan |
United States |
Switzerland |
Finland |
France |
Germany |
Italy |
Netherlands |
Norway |
Spain |
Sweden |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The final date on which data were or are expected to be collected, ie, the last visit of the last participant in the study |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 24 |