Primary:- To assess the effect of TAK-861 on EDS as measured by sleep latency from the MWT.Secondary:- 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…
ID
Source
Brief title
Condition
- Sleep disturbances (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from baseline to Week 8 in mean sleep latency from the MWT.
Secondary outcome
- Change from baseline to Week 8 in ESS total score.
- Occurrence of at least 1 TEAE.
For additional / exploratory endpoints please refer to the study protocol.
Background summary
This study is designed to evaluate the efficacy, safety, and tolerability of
multiple oral doses of TAK-861 in participants with narcolepsy without
cataplexy (narcolepsy type 2 [NT2]).
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. The available nonclinical
information and emerging clinical safety, tolerability, and PK profiles of
single and multiple doses of TAK-861 in healthy participants in the
TAK-861-1001 study support this study.
Study objective
Primary:
- To assess the effect of TAK-861 on EDS as measured by sleep latency from the
MWT.
Secondary:
- 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.
Please refer to the study protocol for additional / exploratory objectives.
Study design
This is a randomized, double-blind, placebo-controlled, multicenter, 8-week
parallel group study to evaluate the efficacy, safety, and tolerability of 2
oral dose regimens of TAK-861.
Approximately 60 (male and female) participants with NT2, who satisfy the
inclusion and exclusion criteria, will be randomized such that a participant
has an equal chance of being assigned to any 1 of 3 arms: 2 TAK-861 dose
regimens or matching placebo. Randomization will be stratified by region.
Starting on the morning of Day 1, the study drug will be administered at
approximately the same time each day for 8 weeks.
Participants who have provided informed consent will complete a screening
period of up to 45 days (see protocol body, Section 6.8.1 for different washout
periods) to washout any NT2 medication (if applicable). Participants will be
asked to complete an eDiary, starting from the initial screening visit, no
later than Day -16.
Participants will remain confined overnight at the study site during the
following times:
- Days -2 to 1 (1 mandatory overnight at Day -2; 1 optional overnight at Day
-1).
- Days 27 to 28 (1 overnight).
- Days 55 to 56 (1 overnight).
After the Week 8 visit, participants will have the option to participate in a
long-term extension (LTE) study under a separate protocol (assuming protocol is
open for enrollment). Participants who enroll in the LTE study will not have
follow-up visits captured under this study protocol.
For participants who do not participate in the LTE study, every effort should
be deployed to have them complete a first follow-up visit approximately 7 days
after the final study drug intake and a second follow-up visit (home healthcare
visit) approximately 28 days after the final study drug intake. For
participants who early terminate the study, every effort should be deployed to
have them complete an early termination visit as soon as possible and a
follow-up visit (in-clinic visit or home healthcare visit if available)
approximately 28 days after the last dose of study drug. Participants not
participating in the LTE study can restart their discontinued medications after
the first follow-up visit or early termination visit.
Intervention
The following treatments will be administered orally:
• TAK-861 Dose Regimen 1: 2 mg twice daily approximately 3 hours apart
• TAK-861 Dose Regimen 2: 7 mg once daily (QD) or 2 mg followed by 5 mg
approximately 3 hours apart
• Matching placebo
Dose Regimen 2 (7 mg total daily dose) will be administered as either 7 mg QD
or 2 mg followed by 5 mg; the decision will be made before randomization of the
first participant.
Study treatment will be administered at approximately 8 am and 11 am.
(Participants assigned to a QD dose regimen will receive placebo for the second
dose.) Study treatment will be administered for 8 weeks.
Study burden and risks
Section E 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 IB 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.
Hayden Avenue 95
Lexington MA 02421
US
Hayden Avenue 95
Lexington MA 02421
US
Listed location countries
Age
Inclusion criteria
1. The participant is aged 18 to 70 years, inclusive, at the time of signing
the informed consent form (ICF).
2. The participant has an International Classification of Sleep Disorders, 3rd
edition (ICSD-3) diagnosis of NT2 by preceding polysomnography (PSG)/ multiple
sleep latency test (MSLT), performed within the past 5 years.
Note: If there is a potential participant with NT2 for whom a diagnostic
nocturnal polysomnography (nPSG)/MSLT was performed more than 5 years ago or is
not available, the site may repeat the diagnostic PSG/MSLT.
Exclusion criteria
1. The participant has a current medical disorder, other than narcolepsy
without cataplexy, associated with EDS.
2. The participant has 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).
3. 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 visit.)
d. Current active major depressive episode (MDE) or who have had an active MDE
in the past 6 months.
4. The participant has a history of cerebral ischemia, transient ischemic
attack (<5 years ago), intracranial aneurysm, or arteriovenous malformation.
5. The participant had major surgery or donated or lost 1 unit of blood
(approximately 500 mL) within 4 weeks before the screening visit.
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 |
|---|---|
| EudraCT | EUCTR2022-002966-34-NL |
| ClinicalTrials.gov | NCT05687916 |
| CCMO | NL82934.100.22 |