| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Narcolepsy with cataplexy (Narcolepsy Type 1) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Narcolepsy with cataplexy (Narcolepsy Type 1) |
|
| 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 |
|
| 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 excessive daytime sleepiness (EDS) as measured by sleep latency from the Maintenance of Wakefulness Test (MWT) |
|
| 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 assess the effect of TAK-861 on cataplexy as assessed by the weekly cataplexy rate (WCR).
- To evaluate the safety and tolerability of TAK-861.
|
|
| 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.
3. The participant is aged 18 to 70 years, inclusive, at the time of signing the ICF.
4. The participant has body mass index within the range 18 to 40 kg/m2 (inclusive)
5. The participant has an ICSD-3 diagnosis of NT1 by polysomnography (PSG)/Multiple Sleep Latency Test (MSLT), performed within the past 10 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 NT1 for whom a diagnostic nPSG/MSLT was performed more than 10 years ago or is not available, the site may repeat the diagnostic PSG/MSLT before Day -2.
Note: For participants with results from a CSF test indicating an OX/hypocretin-1 concentration of ≤110 pg/mL (or less than one-third of the mean values obtained in normal participants within the same standardized assay), the PSG/MSLT requirement may be waived after a discussion with the sponsor or designee.
6. The participant has an ESS score >12 on Day -1.
7. The participant has ≥4 partial and/or complete episodes of cataplexy/week (WCR), calculated as the weekly average over 14 days (Days -16 to -3 of the screening period). Before the start of WCR recording, participants must complete washout of anticataplexy medications (see protocol body, Section 6.8.1 for washout requirements for specific medications). Participants must complete self-reported cataplexy questions in the ediary for at least 11 of 14 days during Days -16 to -3, to be considered compliant. In cases where the e-diary becomes unavailable, the study site may use alternative methods to collect these data with approval from the
sponsor or designee.
8. The participant is positive for the HLA genotype HLA-DQB1*06:02 (positive results for either homozygous or heterozygous alleles will be considered “positive” and acceptable) or results from CSF testing indicate the participant’s CSF OX/hypocretin-1 concentration is <110 pg/mL (or less than one-third of the mean values obtained in normal participants within the same standardized assay).
Note: Previous HLA results are acceptable if available for review by the PI and provided for inclusion in the electronic case report form.
9. 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.
10. The participant agrees to follow the birth control requirements. |
|
| E.4 | Principal exclusion criteria |
1. The participant has a current medical disorder, other than narcolepsy with cataplexy, associated with EDS.
a) This includes restless legs syndrome/periodic limb movement disorder that has a significant impact on daytime sleepiness.
b) Participants with clinically significant moderate-to-severe obstructive sleep apnea may be eligible if they are compliant with continuous positive airway pressure (CPAP), defined as having at least 4 hours of CPAP use per night on at least 70% of nights for approximately 1 month before randomization (assessed by
machine tracking time) and have apnea hypopnea index (AHI) ≤10 with CPAP or other modes of positive airway pressure.
c) For all participants, past PSG data demonstrating any of the following is exclusionary: AHI ≥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 (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [more than once per week] occurrence of heartburn, or any surgical intervention). 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 Diagnostic and Statistical Manual of Mental Disorders,5th Edition (DSM-5).
c) Current diagnosis or history of substance use disorder as defined in the DSM-5.
Note: If the history of substance use disorder is more than 12 months before baseline, the participant may be allowed to enroll in the study after consultation with the sponsor or designee. (Participant must also have negative urine drug screen at the screening and Day -2 visits.)
d) Current active major depressive episode (MDE) or who have had an active MDE in the past 6 months.
Note: Neurodevelopmental disorders (eg, attention deficit hyperactivity disease) are not excluded unless severity does not allow termination of prohibited medications (see protocol body, Section 6.8.1 for list of restricted medications).
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 (eg, food, drug, latex allergy) 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.
for exclusion criteria 14-42 please refer to the study protocol |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline to Week 8 in mean sleep latency from the MWT |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Change from baseline to Week 8 in ESS total score
- WCR at week 8
- Occurrence of at least 1 treatment-emergent adverse event (TEAE) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | 5 |
| 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 | 29 |
| 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 |
|
| 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
|
| The final date on which data were or are expected to be collected, ie, the last visit of the last participant in the study. |
|
| 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 | 4 |
| E.8.9.1 | In the Member State concerned days | 5 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 5 |
Print
