Clinical Trial Results:
A Randomized, Double-Blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-861 for the Treatment of Narcolepsy without Cataplexy (Narcolepsy Type 2)
Summary
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EudraCT number |
2022-002966-34 |
Trial protocol |
NO SE FR IT ES FI |
Global end of trial date |
25 Dec 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Dec 2024
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First version publication date |
29 Dec 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TAK-861-2002
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05687916 | ||
WHO universal trial number (UTN) |
U1111-1282-8382 | ||
Other trial identifiers |
jRCT: jRCT2031230050 | ||
Sponsors
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Sponsor organisation name |
Takeda Development Center Americas, Inc.
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Sponsor organisation address |
95 Hayden Avenue, Lexington, Massachusetts, United States, 02421
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Public contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Scientific contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Dec 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Dec 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of the study was to assess the effect of TAK-861 on excessive daytime sleepiness (EDS) as measured by sleep latency from the Maintenance of Wakefulness Test (MWT).
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Protection of trial subjects |
All study participants were required to read and sign an informed consent form (ICF).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Jan 2023
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 41
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Italy: 6
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Country: Number of subjects enrolled |
Spain: 15
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Country: Number of subjects enrolled |
Japan: 8
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Worldwide total number of subjects |
71
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EEA total number of subjects |
22
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
70
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants took part in the study at 28 investigative sites globally from 09 January 2023 to 25 December 2023. | ||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Participants with a diagnosis of narcolepsy type 2 (NT2) were enrolled in the study to receive either TAK-861 or placebo. | ||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
No
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||
Arm description |
Participants received placebo tablets matching TAK-861, orally, BID, from Days 1 to 56. | ||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were administered TAK-861 matching placebo tablet twice a day 3 hours apart or once a day as required.
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Arm title
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TAK-861 2 mg BID | ||||||||||||||||||||||||||||||||
Arm description |
Participants received TAK-861 2 mg, orally, BID, from Days 1 to 56. | ||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
TAK-861
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Investigational medicinal product code |
TAK-861
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were administered TAK-861 2 milligrams (mg) tablets twice a day 3 hours apart.
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Arm title
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TAK-861 2 mg and 5 mg | ||||||||||||||||||||||||||||||||
Arm description |
Participants received TAK-861 2 mg followed by the 5 mg dose, orally, from Days 1 to 56. | ||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||
Investigational medicinal product name |
TAK-861
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Investigational medicinal product code |
TAK-861
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were administered TAK-861 2 mg followed by 5 mg 3 hours apart or TAK-861 7mg once daily.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo tablets matching TAK-861, orally, BID, from Days 1 to 56. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TAK-861 2 mg BID
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Reporting group description |
Participants received TAK-861 2 mg, orally, BID, from Days 1 to 56. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TAK-861 2 mg and 5 mg
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Reporting group description |
Participants received TAK-861 2 mg followed by the 5 mg dose, orally, from Days 1 to 56. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo tablets matching TAK-861, orally, BID, from Days 1 to 56. | ||
Reporting group title |
TAK-861 2 mg BID
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Reporting group description |
Participants received TAK-861 2 mg, orally, BID, from Days 1 to 56. | ||
Reporting group title |
TAK-861 2 mg and 5 mg
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Reporting group description |
Participants received TAK-861 2 mg followed by the 5 mg dose, orally, from Days 1 to 56. |
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End point title |
Change from Baseline in the Average Sleep Latency as Determined From the MWT at Week 8 | ||||||||||||||||
End point description |
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. 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. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Primary
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End point timeframe |
Baseline, Week 8
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Statistical analysis title |
Average Sleep Latency | ||||||||||||||||
Comparison groups |
Placebo v TAK-861 2 mg BID
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.989 [1] | ||||||||||||||||
Method |
MMRM | ||||||||||||||||
Parameter type |
LS Mean Difference Estimate | ||||||||||||||||
Point estimate |
-0.24
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-6.67 | ||||||||||||||||
upper limit |
6.18 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
3.277
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Notes [1] - The analysis used a linear MMRM with fixed effects for Baseline, age, prior use of narcolepsy medications, treatment, visit, and treatment-by-visit interaction as covariates. The p-value reported is adjusted for multiplicity. |
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Statistical analysis title |
Average Sleep Latency | ||||||||||||||||
Comparison groups |
Placebo v TAK-861 2 mg and 5 mg
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Number of subjects included in analysis |
43
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.916 [2] | ||||||||||||||||
Method |
MMRM | ||||||||||||||||
Parameter type |
LS Mean Difference Estimate | ||||||||||||||||
Point estimate |
2.4
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-3.93 | ||||||||||||||||
upper limit |
8.72 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
3.227
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Notes [2] - The analysis used a linear MMRM with fixed effects for Baseline, age, prior use of narcolepsy medications, treatment, visit, and treatment-by-visit interaction as covariates. The p-value reported is adjusted for multiplicity. |
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End point title |
Number of Participants with at Least One Treatment Emergent Adverse Event (TEAE) | ||||||||||||
End point description |
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. The Safety Analysis Set included all participants who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
From first dose of the study drug up to end of the study (up to 3 months)
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 8 | ||||||||||||||||
End point description |
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. 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. Subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8
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Statistical analysis title |
Epworth Sleepiness Scale (ESS) Total Score | ||||||||||||||||
Comparison groups |
Placebo v TAK-861 2 mg and 5 mg
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Number of subjects included in analysis |
42
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.216 [3] | ||||||||||||||||
Method |
MMRM | ||||||||||||||||
Parameter type |
LS Mean Difference Estimate | ||||||||||||||||
Point estimate |
-3.06
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-6.18 | ||||||||||||||||
upper limit |
0.06 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.59
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Notes [3] - The analysis used a linear MMRM with fixed effects for Baseline, age, prior use of narcolepsy medications, treatment, visit, and treatment-by-visit interaction as covariates. The p-value reported is adjusted for multiplicity. |
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Statistical analysis title |
Epworth Sleepiness Scale (ESS) Total Score | ||||||||||||||||
Comparison groups |
Placebo v TAK-861 2 mg BID
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.989 [4] | ||||||||||||||||
Method |
MMRM | ||||||||||||||||
Parameter type |
LS Mean Difference Estimate | ||||||||||||||||
Point estimate |
-0.32
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-3.57 | ||||||||||||||||
upper limit |
2.92 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.656
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Notes [4] - The analysis used a linear MMRM with fixed effects for Baseline, age, prior use of narcolepsy medications, treatment, visit, and treatment-by-visit interaction as covariates. The p-value reported is adjusted for multiplicity. |
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of the study drug up to end of the study (up to 3 months)
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Adverse event reporting additional description |
The Safety Analysis Set included all participants who received at least 1 dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.1
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo tablets (]matching TAK-861, orally, twice daily (BID), from Days 1 to 56. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TAK-861 2 mg and 5 mg
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Reporting group description |
Participants received TAK-861 2 mg followed by the 5 mg dose, orally, from Days 1 to 56. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TAK-861 2 mg BID
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Reporting group description |
Participants received TAK-861 2 milligrams (mg), orally, BID, from Days 1 to 56. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |