| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Narcolepsy with Cataplexy (Type 1) and Narcolepsy without Cataplexy (Type 2) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Narcolepsy with Cataplexy (Type 1) and Narcolepsy without Cataplexy (Type 2) |
|
| 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 evaluate the long-term safety and tolerability of TAK-861. |
|
| E.2.2 | Secondary objectives of the trial |
• To assess the effect of TAK-861 on excessive daytime sleepiness (EDS) as assessed by the mean sleep latency from the Maintenance of Wakefulness Test(MWT)
• 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) (participants with narcolepsy type 1
[NT1] only). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Informed Consent
1. 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. Participant has provided informed consent (that is, in writing, documented via a signed and dated informed consent form (ICF) and/or electronic consent [eConsent]) and any required privacy authorization before the initiation of any study procedures.
Type of Participant and Disease Characteristics
3. Participant with a diagnosis of narcolepsy who has completed a controlled study with TAK-861 (including participants diagnosed with NT1 or NT2) and for whom the investigator has no clinical objection to their enrollment. Additionally, a rare exception may be granted by the sponsor or designee for a participant who was unable to complete a previous TAK-861 controlled study conducted in participants with narcolepsy.
Contraception
4. The participant agrees to follow the birth control requirements |
|
| E.4 | Principal exclusion criteria |
Medical Conditions
1. Participant has a moderate or severe ongoing (TEAE) related to the study drug from the parent study or discontinued because of TEAEs in the parent study.
Prior/Concomitant Therapy
2. Participant used disallowed medication during the parent study and is unable to refrain from or anticipates using excluded medications.
Diagnostic Assessments
3. Participant has a (BP) >160 mm Hg (systolic) or >100 mm Hg (diastolic) at the final collection point in any prior controlled study without a dosing gap. The participant may have a history of hypertension and be on antihypertensive medication treatment as long as the BP values are below these criteria. BP measurements should be obtained after the participant has been semirecumbent (lying down with the head of the bed at 30 degrease) for a minimum of 5 minutes. BP will be repeated 3 times, with a minimum of 2 minutes between assessments. The median BP (of 3 assessments) obtained will be used for assessing participant eligibility.
4. Participant has a resting HR outside of the range of 40 to 100 beats per minute, confirmed on repeat testing within a maximum of 30 minutes at assessment at screening.
5. Participant has an ECG with a (QTcF) interval>450 ms (men) or >470 ms (women) at screening.
6. Participant has (ALT) and (AST) >1.5 times the (ULN) at multiple visits in the parent study and the findings are of clinical significance, per investigator or sponsor opinion, or ALT/AST >1.5 times ULN during the screening period for participants with a dosing gap.
7. Participant’s renal creatinine clearance is ≤50 mL/min.
8. Participant has a positive urine screen for drugs of abuse (findings confirmed) and/or positive alcohol test during any visit in their prior TAK-861 study, or during the screening period for participants with a dosing gap. Products containing cannabidiol are allowed throughout the study, at the discretion of the investigator.
9. Participant has a positive pregnancy test at screening or is a lactating/breastfeeding woman.
10. Participant has a risk of suicide according to endorsement of item 4 or 5 on the C-SSRS Since Last Visit (C-SSRS) on any visit in the prior study, or has positive answers on item 4 or 5 on the Screening/Baseline C-SSRS Lifetime (based on the past year) during the screening assessment for participants with a dosing gap.
Other Exclusion Criteria
11. Participant consumes excessive amounts of caffeine, defined as greater than 600 mg of caffeine of coffee, tea, cola, energy drinks, or other caffeinated beverages per day (1 cup of coffee is approximately 120 mg).
12. Participant is unwilling to refrain from drivingand/or operating dangerous or hazardous machinery during times of heightened sleepiness or fatigue as well as during times of medication weaning/changes, or is unwilling to adhere to local regulations and any PI guidance restricting driving.
Participants with a Dosing GapUp to 3 Months
Additional exclusion criteria for participants who have completed their parent study and who are not able to directly roll over into the current study (ie, for whom there is a dosing gap), are as follows:
13. Participant has participated in another investigational drug study, in which they received the investigational drug other than TAK-861, within 60 days (or 6 months if participant may have received an investigational biologic product). The interval window from the parent study will be derived from the date of the last study procedure in the parent study to the screening visit of TAK-861-2003.
14. Participant is unable to discontinue, or refrain from using excluded medications for the duration of the study, including those used for the treatment of narcolepsy. Participant must be willing to complete specified washout periods before the first dose of study drug
Medical Conditions
15. The participant has a current medical disorder, other than narcolepsy with or without cataplexy, associated with EDS.
a. Participants with NT1 with clinically significant, moderate-to-severe obstructive sleep apnea may be eligible if they are compliant with (PAP), defined as having at least 4 hours of PAP use per night on at least 70% of nights for approximately 1 month before Day 1 (assessed by machine tracking time) and have (AHI) ≤10 with PAP or other modes of positive airway pressure.
16. Participant has a known hypersensitivity to any component of the formulation of TAK-861 or related compounds.
17. Participant has current active major depressive episode (MDE) or has had an MDE in the past 6 months.
18. Participant has developed (within the last 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).
For further exclusion criteria no 19-27 please refer to the protocol |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Occurrence of at least 1 treatment-emergent adverse event (TEAE). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Day 395, 425, 485, 515, 575, 605, 665, 695 |
|
| E.5.2 | Secondary end point(s) |
• Change from baseline in the parent study in MWT mean sleep latency.
• Change from baseline in the parent study in ESS total score
• Change from baseline in the parent study in WCR using the patient-reported cataplexy diary (participants with NT1 only) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Day 182
- Day 14, 28, 56, 84, 182, 266, 364, 448, 546, 630. 728
- Day 69 to 84; 167 to 182; 251 to 266; 350to 364; 531 to 546; 715 to 728; 728 to 735 |
|
| 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 | No |
| E.6.6 | Pharmacokinetic | No |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | Yes |
| 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 | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| 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 |
| Finland |
| France |
| Sweden |
| Netherlands |
| Spain |
| Switzerland |
| Germany |
| Italy |
| Norway |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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 end of study is defined as 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 | 3 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 4 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| 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 | 4 |
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