Narcolepsy Type 2
Conditions
Keywords
Drug Therapy
Brief summary
The main aim is to evaluate the effect of TAK-861 on symptoms of narcolepsy, including excessive daytime sleepiness (EDS) as measured by sleep latency from the Maintenance of Wakefulness Test (MWT). The study will enroll approximately 60 participants and they will be randomly assigned to 3 groups (20 per group) to take one of two different doses of TAK-861 or a placebo. All the participants will receive the treatment for 8 weeks. Participants will be asked to complete some questionnaires during the study. This trial will be conducted in North America, Europe, and Asia Pacific.
Detailed description
The drug being tested in this study is called TAK-861. TAK-861 is being tested to treat people who have narcolepsy without cataplexy \[Narcolepsy Type 2 (NT2)\]. This study will evaluate the efficacy, safety, and tolerability of 2 oral doses of TAK-861. The study will enroll approximately 60 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): * TAK-861 Dose 1 * TAK-861 Dose 2 * Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient This is a multi-center trial to be conducted worldwide. The overall time to participate in this study is approximately 18 weeks.
Interventions
DRUGPlacebo
TAK-861 placebo matching tablets.
DRUGTAK-861 2 mg
TAK-861 2 mg tablets.
DRUGTAK-861 2 mg and 5 mg
TAK-861 2 mg and 5 mg tablets.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
\- The participant is aged 18 to 70 years, inclusive, at the time of signing the informed consent form (ICF). Note: In Japan, participants aged 16 to 70 years, inclusive, may be included. \- 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
* The participant has a current medical disorder, other than narcolepsy without cataplexy, associated with EDS. * 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). * The participant has one or more of the following psychiatric disorders: 1. Any current unstable psychiatric disorder. 2. 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). 3. 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.) 4. Current active major depressive episode (MDE) or who have had an active MDE in the past 6 months. * The participant has a history of cerebral ischemia, transient ischemic attack (\<5 years ago), intracranial aneurysm, or arteriovenous malformation. * The participant had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks before the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average Sleep Latency as Determined From the MWT at Week 8 | Baseline, Week 8 | The MWT is a validated, objective measure that evaluates a participant's ability to remain awake under soporific conditions for a defined period. During each MWT session (1 session = 40 minutes), participants were instructed to sit quietly and remain awake for as long as possible. Sleep latency in each session was recorded on EEG. If no sleep was observed according to these rules, then the latency was defined as 40 minutes. The linear mixed effects model for repeated measures (MMRM) was used for analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 8 | Baseline, Week 8 | The ESS is a subjective, self-administered, validated scale (scored 0 to 3) to respond to each of the 8 questions of daily life that asks participants how likely they are to fall asleep in those situations. The scores are summed to give an overall score of 0 to 24. Higher scores indicate stronger subjective daytime sleepiness, and scores below 10 are considered to be within the normal range. The MMRM was used for analysis. |
| Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) | From first dose of the study drug up to end of the study (up to 3 months) | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of the study intervention, whether or not the occurrence is considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE whose date of onset occurred on or after the first dose of study drug. |
Countries
Australia, Finland, France, Germany, Italy, Japan, Netherlands, Norway, Spain, Sweden, Switzerland, United States
Participant flow
Recruitment details
Participants took part in the study at 28 investigative sites globally from 09 January 2023 to 25 December 2023.
Pre-assignment details
Participants with a diagnosis of narcolepsy type 2 (NT2) were enrolled in the study to receive either TAK-861 or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo tablets matching TAK-861, orally, BID, from Days 1 to 56. | 24 |
| TAK-861 2 mg BID Participants received TAK-861 2 mg, orally, BID, from Days 1 to 56. | 23 |
| TAK-861 2 mg and 5 mg Participants received TAK-861 2 mg followed by the 5 mg dose, orally, from Days 1 to 56. | 24 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 2 | 1 |
| Overall Study | Reason not Specified | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | TAK-861 2 mg BID | TAK-861 2 mg and 5 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 37.0 years STANDARD_DEVIATION 12.69 | 34.9 years STANDARD_DEVIATION 9.77 | 36.8 years STANDARD_DEVIATION 12.61 | 36.2 years STANDARD_DEVIATION 11.66 |
| Average Sleep Latency From the Maintenance of Wakefulness Test (MWT) | 10.8 minutes STANDARD_DEVIATION 8.72 | 9.9 minutes STANDARD_DEVIATION 10.29 | 8.4 minutes STANDARD_DEVIATION 8.26 | 9.7 minutes STANDARD_DEVIATION 9.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 5 Participants | 2 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 18 Participants | 20 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 1 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 13 Participants | 19 Participants | 14 Participants | 46 Participants |
| Sex: Female, Male Female | 18 Participants | 14 Participants | 17 Participants | 49 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 7 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 23 | 0 / 24 |
| other Total, other adverse events | 2 / 24 | 7 / 23 | 14 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 | 0 / 24 |
Outcome results
Primary
Change From Baseline in the Average Sleep Latency as Determined From the MWT at Week 8
The MWT is a validated, objective measure that evaluates a participant's ability to remain awake under soporific conditions for a defined period. During each MWT session (1 session = 40 minutes), participants were instructed to sit quietly and remain awake for as long as possible. Sleep latency in each session was recorded on EEG. If no sleep was observed according to these rules, then the latency was defined as 40 minutes. The linear mixed effects model for repeated measures (MMRM) was used for analysis.
Time frame: Baseline, Week 8
Population: The Full Analysis Set included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 post-dose efficacy measurement. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Average Sleep Latency as Determined From the MWT at Week 8 | 2.14 minutes | Standard Error 2.246 |
| TAK-861 2 mg BID | Change From Baseline in the Average Sleep Latency as Determined From the MWT at Week 8 | 1.90 minutes | Standard Error 2.384 |
| TAK-861 2 mg and 5 mg | Change From Baseline in the Average Sleep Latency as Determined From the MWT at Week 8 | 4.54 minutes | Standard Error 2.3 |
p-value: =0.98995% CI: [-6.67, 6.18]MMRM
p-value: =0.91695% CI: [-3.93, 8.72]MMRM
Secondary
Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 8
The ESS is a subjective, self-administered, validated scale (scored 0 to 3) to respond to each of the 8 questions of daily life that asks participants how likely they are to fall asleep in those situations. The scores are summed to give an overall score of 0 to 24. Higher scores indicate stronger subjective daytime sleepiness, and scores below 10 are considered to be within the normal range. The MMRM was used for analysis.
Time frame: Baseline, Week 8
Population: The Full Analysis Set included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 post-dose efficacy measurement. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 8 | -3.39 score on a scale | Standard Error 1.14 |
| TAK-861 2 mg BID | Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 8 | -3.71 score on a scale | Standard Error 1.206 |
| TAK-861 2 mg and 5 mg | Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 8 | -6.45 score on a scale | Standard Error 1.121 |
p-value: =0.98995% CI: [-3.57, 2.92]MMRM
p-value: =0.21695% CI: [-6.18, 0.06]MMRM
Secondary
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of the study intervention, whether or not the occurrence is considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE whose date of onset occurred on or after the first dose of study drug.
Time frame: From first dose of the study drug up to end of the study (up to 3 months)
Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) | 8 Participants |
| TAK-861 2 mg BID | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) | 10 Participants |
| TAK-861 2 mg and 5 mg | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) | 18 Participants |