This study has been transitioned to CTIS with ID 2023-508462-15-00 check the CTIS register for the current data. To evaluate the long-term safety and tolerability of TAK-861.
ID
Source
Brief title
Condition
- Sleep disturbances (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Occurrence of at least 1 treatment-emergent adverse event (TEAE).
Secondary outcome
- 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).
Background summary
The current study is a dose-blind, long-term extension (LTE) study to collect
and evaluate long-term safety and tolerability data of TAK-861 in participants
with narcolepsy type 1 (NT1) or narcolepsy type 2 (NT2) who were exposed to
previously tested doses of TAK-861 and then treated for up to another 104 weeks
(2 years).
Narcolepsy without cataplexy, or NT2, has been defined in the International
Classification of Sleep Disorders, 3rd Edition (ICSD-3) criteria as having EDS
with mean sleep latency of <=8 minutes and 2 or more sleep onset REM periods
(SOREMPs) on Multiple Sleep Latency Test (MSLT) (or with 1 SOREMP on preceding
polysomnography (PSG) replacing 1 SOREMP on MSLT). Patients with NT2 do not
have cataplexy, and cerebrospinal fluid (CSF) levels of orexin (OX) are greater
than 110 pg/mL, or greater than one-third of the normal average. The presumed
pathophysiology of NT2 is unclear. However, as many as 30% of patients with
narcolepsy without cataplexy are found to have CSF OX levels that are lower
than normal.
TAK-861 is a selective agonist of OX2R that has demonstrated wake-promoting
effects even in the absence of OX deficiency.
Nonclinical pharmacology studies showed wake-promoting effects of TAK-861 in a
murine narcolepsy model and also in mice and nonhuman primates with no known OX
deficiency. In TAK-861-1002, single doses of TAK 861 40 mg and 15 mg
demonstrated a significant improvement in the objective and subjective measures
of wakefulness assessed in an acute sleep delayed paradigm model in healthy
adults. Review of available nonclinical and clinical data, including the
nonserious, mild TEAEs reported in ongoing Study TAK-861-1001 and TAK-861-1002,
supports a favorable benefit-risk ratio for this study with TAK-861. Refer to
the latest version of the TAK-861 Investigators Brochure for the overall
benefit/risk assessment and the most current information regarding drug
metabolism, PK, efficacy, and safety of TAK-861.
Study objective
This study has been transitioned to CTIS with ID 2023-508462-15-00 check the CTIS register for the current data.
To evaluate the long-term safety and tolerability of TAK-861.
Study design
This is a phase 2/3 multicenter, dose-blind, LTE study of TAK-861. Participants
from controlled studies conducted with TAK-861, who have up to a 3-month dosing
gap between the parent study and screening period for TAK-861-2003, will be
eligible to participate in this study (eg,TAK-861-2001 and other studies).
Intervention
For participants with NT1:
- TAK-861 Dose Regimen 1: 0.5 mg twice daily (BID), approximately 3 hours apart.
- TAK-861 Dose Regimen 2: 2 mg twice daily, approximately 3 hours apart.
- TAK-861 Dose Regimen 3: 2 mg followed by 5 mg, approximately 3 hours apart.
- TAK-861 Dose Regimen 4: 7 mg once daily (QD).
For participants with NT2:
- TAK-861 Dose Regimen 1: 2 mg twice daily, approximately 3 hours apart.
- TAK-861 Dose Regimen 2: 2 mg followed by 5 mg, approximately 3 hours apart.
Study burden and risks
Section E of this ABR form describes the burden and risks of participation as
well as the (possible) benefit.
Review of available nonclinical and clinical data, including the nonserious,
mild TEAEs reported in ongoing Study TAK-861-1001 and TAK-861-1002, supports a
favorable benefit-risk ratio for this study with TAK 861. Refer to the latest
version of the TAK-861 Investigators Brochure for the overall benefit/risk
assessment and the most current information regarding drug metabolism, PK,
efficacy, and safety of TAK 861.
Please refer to protocol section 2.3 for a detailed benefit/risk assessment.
95 Hayden Avenue -
Lexington MA 02142
US
95 Hayden Avenue -
Lexington MA 02142
US
Listed location countries
Age
Inclusion criteria
1. 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.
Exclusion criteria
1. Participant has a moderate or severe ongoing treatment emergent adverse
event (TEAE) related to the study drug from the parent study or discontinued
because of TEAEs in the parent study.
2. 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.
3. Participant has a risk of suicide according to endorsement of item 4 or 5 on
the Columbia Suicide Severity Rating Scale (C-SSRS) on any visit in the parent
TAK-861 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.
4. Participant has alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) >1.5 times the upper limit of normal (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.
5. Participant has a current medical disorder, other than narcolepsy with or
without cataplexy, associated with excessive daytime sleepiness (EDS).
6. Participant has current active major depressive episode (MDE) or has had an
active MDE in the past 6 months.
7. Participant has developed (within the last 6 months) gastrointestinal
disease that is expected to influence the absorption of drugs (i.e., a history
of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis,
frequent [more than once per week] occurrence of heartburn, or any surgical
intervention).
8. Participant has epilepsy or history of seizure.
9. Participant has any other medical condition, such as anxiety, depression,
heart disease, or significant hepatic, pulmonary, or renal disease, that
requires them to take excluded medications.
10. Participant has a history of cerebral ischemia, transient ischemic attack
(<5 years ago), or cerebral hemorrhage.
11. Participant has a history of myocardial infarction, clinically significant
coronary artery disease, clinically significant angina, clinically significant
cardiac rhythm abnormality, or heart failure.
12. 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 skin cancer.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-508462-15-00 |
| EudraCT | EUCTR2022-002965-13-NL |
| CCMO | NL83126.056.22 |