Narcolepsy Type 1 (NT 1)
Conditions
Keywords
Drug Therapy
Brief summary
Adults with narcolepsy who have completed the TAK-994-1501 study will be able to take part in this study. The main aim of this study is to check if participants have side effects from TAK-994. Participants will take one of 3 different TAK-994 dose for 8 weeks. Then, half the participants will continue with their dose of TAK-994 and half will take a placebo. In this study, a placebo will look like a TAK-994 tablet but will not have any medicine in it. Participants will take TAK-994 or placebo for 4 weeks. Participants will visit the clinic for a final check-up 2 weeks after their last dose of TAK-994 or placebo. The study doctors will check for side effects from TAK-994 and placebo throughout the study. Participants will continue to record any narcolepsy symptoms as they did in Part B of the TAK 994-1501 study.
Detailed description
The drug being tested in the study is called TAK-994. TAK-994, is being tested to treat participants with NT1. Participants who completed Part B of TAK-994-1501(NCT04096560) will be eligible for enrollment in this study. This study will enroll approximately 112 patients to receive one of three different TAK 994 dose for 8 weeks (active drug extension period). Participants will be randomly assigned to one of these different TAK 994 doses which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). Following the 8-week Active Drug Extension Period, participants will continue into a 4-week Double-blind Randomized Withdrawal Period and will receive TAK-994 or Placebo. Participants randomized to TAK-994 will continue to receive the same dose as before. This multi-center trial will be conducted worldwide. The duration of treatment in this study is 12 weeks plus a 2 week safety follow up period. Participants will visit the clinic 10 times after the first dosing.
Interventions
DRUGTAK-994
TAK-994 tablets.
DRUGPlacebo
Placebo-matching tablets.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1\. Participant with a diagnosis of Narcolepsy Type 1 (NT1) who has completed TAK-994-1501 Part B before enrollment (which will occur immediately following the final TAK-994-1501 assessments), and for whom the investigator has no clinical objection they be enrolled.
Exclusion criteria
1\. Participant has a clinically significant moderate or severe ongoing AE related to the study drug from the prior study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period | Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8) | MAV criteria for ECG were: Heart rate \<40 bpm, \>115 bpm; PR interval ≤80 milliseconds (msec), ≥200 msec; QT interval with Fridericia correction method (QTcF) Interval ≤300 msec, \>500 msec or ≥30 msec change from baseline and \>450 msec; QRS duration ≤80 msec, ≥180 msec. Only categories with at least one participant with event are reported. |
| Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) During the Active Drug Extension Period | Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8) | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participants administered a drug; it does not necessarily have to have a causal relationship with this treatment. 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 is defined as an AE with an onset that occurs after receiving study drug. |
| Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8) | Clinical laboratory tests included hematology, serum chemistry, and urinalysis. MAV criteria: Hemoglobin \<0.8×lower limit of normal (LLN), \>1.2×upper limit of normal (ULN); Hematocrit \<0.8×LLN, \>1.2×ULN; Red blood cells (RBC) count \<0.8×LLN, \>1.2×ULN; White blood cells (WBC) count \<0.5xLLN, \>1.5xULN; Platelet count \<75x10\^9/liter (L), \>600x10\^9/L; alanine aminotransferase (ALT) \>3xULN; aspartate aminotransferase (AST) \>3xULN; gamma-glutamyl transferase (GGT) \>3xULN; Alkaline phosphatase \>3xULN; Total bilirubin \>1.5xULN; Albumin \<25 grams per liter (g/L); Total protein \<0.8xLLN, \>1.2xULN; Creatinine \>1.5xULN; Blood urea nitrogen \>40 milligrams per deciliters (mg/dL); Sodium \<130 milliequivalents per liter (mEq/L), \>150 mEq/L; Potassium \<3.0 millimoles per liter (mmol/L), \>5.3 mmol/L; creatine phosphokinase (CPK) \>3xULN; Glucose \<50 mg/dL, \>300 mg/dL; Calcium \<7.7 mg/dL, \>11.1 mg/dL. Only categories with at least one participant with event are reported. |
| Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8) | MAV criteria for vital signs were: Pulse \<40 beats per minute (bpm), \>115 bpm; Systolic blood pressure \<90 millimeters of mercury (mmHg), ≥160 mmHg; Diastolic blood pressure \<50 mmHg, ≥100 mmHg, Systolic or Diastolic blood pressure change of \>20, \>30 mmHg from Baseline, Body temperature \>38.5 degree Celsius, Respiratory Rate \>21 breath/minute. Only categories with at least one participant with event are reported. Baseline for this outcome measure is Day 1 of the Active Drug Extension Period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One TEAE During the Double-blind Randomized Withdrawal Period | Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12) | An AE is defined as any untoward medical occurrence in a clinical investigation participants administered a drug; it does not necessarily have to have a causal relationship with this treatment. 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 is defined as an AE with an onset that occurs after receiving study drug. |
| Number of Participants With at Least One Post-dose MAV in Laboratory Test During the Double-blind Randomized Withdrawal Period | Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12) | Clinical laboratory tests included hematology, serum chemistry, and urinalysis. MAV criteria: Hemoglobin \<0.8×LLN, \>1.2×ULN; Hematocrit \<0.8×LLN, \>1.2×ULN; RBC count \<0.8×LLN, \>1.2×ULN; WBC count \<0.5xLLN, \>1.5xULN; Platelet count \<75x10\^9/L, \>600x10\^9/L; ALT \>3xULN; AST \>3xULN; GGT \>3xULN; Alkaline phosphatase \>3xULN; Total bilirubin \>1.5xULN; Albumin \<25 g/L; Total protein \<0.8x LLN, \>1.2xULN; Creatinine \>1.5xULN; Blood urea nitrogen \>40 mg/dL; Sodium \<130 mEq/L, \>150 mEq/L; Potassium \<3.0 mmol/L, \>5.3 mmol/L; CPK \>3xULN; Glucose \<50 mg/dL, \>300 mg/dL; Calcium \<7.7 mg/dL, \>11.1 mg/dL. |
| Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12) | MAV criteria for vital signs were: Pulse \<40 bpm, \>115 bpm; Systolic blood pressure \<90 mmHg, ≥160 mmHg; Diastolic blood pressure \<50 mmHg, ≥100 mmHg, Systolic or Diastolic blood pressure change of \>20, \>30 mmHg from Baseline, Body temperature \>38.5 degree Celsius, Respiratory Rate \>21 breath/minute. Only categories with at least one participant with event are reported. Baseline for this outcome measure is Day 1 of the Double-blind Randomized Withdrawal Period (Day 57 of this study). |
| Number of Participants With at Least One Post-dose MAV for ECG Parameters During the Double-blind Randomized Withdrawal Period | Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12) | MAV criteria for ECG were: Heart rate \<40 bpm, \>115 bpm; PR interval ≤80 msec, ≥200 msec; QTcF Interval ≤300 msec, \>500 msec or ≥30 msec change from baseline and \>450 msec; QRS duration ≤80 msec, ≥180 msec. Only categories with at least one participant with event are reported. |
Countries
Canada, Czechia, Finland, France, Hungary, Italy, Japan, South Korea, Spain, United States
Participant flow
Recruitment details
Participants took part in the study at 13 investigative sites in Spain, Italy, Japan, Korea, and the United States from 30 April 2021 to 03 November 2021 \[early termination date\].
Pre-assignment details
Participants with narcolepsy type 1 (NT 1) who completed Part B of TAK-994-1501(NCT04096560) were enrolled in this study to receive TAK-994 or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Active Drug Extension Period: TAK-994 30 mg TAK-994 30 mg, BID tablets, orally, from Day 1 (Day 57 of previous study) to Day 56 in the Active Drug Extension Period. | 8 |
| Active Drug Extension Period: TAK-994 90 mg TAK-994 90 mg, BID, tablets, orally, from Day 1 (Day 57 of previous study) to Day 56 in the Active Drug Extension Period. | 9 |
| Active Drug Extension Period: TAK-994 180 mg TAK-994 180 mg, BID, tablets, orally, from Day 1 (Day 57 of previous study) to Day 56 in the Active Drug Extension Period. | 9 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Active Drug Extension Period (8 Weeks) | Adverse Event | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
| Active Drug Extension Period (8 Weeks) | Study Terminated by Sponsor (ongoing participants in this period were discontinued) | 3 | 6 | 5 | 0 | 0 | 0 | 0 |
| Active Drug Extension Period (8 Weeks) | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Randomized Withdrawal Period (4 Weeks) | Study Terminated by Sponsor (ongoing participants in this period were discontinued) | 0 | 0 | 0 | 2 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Active Drug Extension Period: TAK-994 30 mg | Total | Active Drug Extension Period: TAK-994 180 mg | Active Drug Extension Period: TAK-994 90 mg |
|---|---|---|---|---|
| Age, Continuous | 31.4 years STANDARD_DEVIATION 12.13 | 30.8 years STANDARD_DEVIATION 10.56 | 29.7 years STANDARD_DEVIATION 11.08 | 31.3 years STANDARD_DEVIATION 9.75 |
| Body Mass Index (BMI) | 28.3 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 5.86 | 27.3 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 5.33 | 25.9 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 5.07 | 27.7 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 5.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 25 Participants | 9 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 163.9 centimeters (cm) STANDARD_DEVIATION 8.39 | 169.8 centimeters (cm) STANDARD_DEVIATION 8.58 | 174.4 centimeters (cm) STANDARD_DEVIATION 6.45 | 170.5 centimeters (cm) STANDARD_DEVIATION 8.24 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 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 | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 18 Participants | 6 Participants | 6 Participants |
| Region of Enrollment Italy | 1 Participants | 9 Participants | 4 Participants | 4 Participants |
| Region of Enrollment Japan | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Korea, South | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Spain | 4 Participants | 5 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 2 Participants | 9 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Female | 7 Participants | 14 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 12 Participants | 6 Participants | 5 Participants |
| Weight | 76.5 kilograms (kg) STANDARD_DEVIATION 18.52 | 79.2 kilograms (kg) STANDARD_DEVIATION 18.68 | 79.1 kilograms (kg) STANDARD_DEVIATION 16.15 | 81.8 kilograms (kg) STANDARD_DEVIATION 22.68 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 9 | 0 / 9 | 0 / 3 | 0 / 1 | 0 / 1 | 0 / 3 |
| other Total, other adverse events | 5 / 8 | 4 / 9 | 3 / 9 | 0 / 3 | 1 / 1 | 0 / 1 | 1 / 3 |
| serious Total, serious adverse events | 0 / 8 | 1 / 9 | 1 / 9 | 0 / 3 | 0 / 1 | 0 / 1 | 0 / 3 |
Outcome results
Primary
Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period
Clinical laboratory tests included hematology, serum chemistry, and urinalysis. MAV criteria: Hemoglobin \<0.8×lower limit of normal (LLN), \>1.2×upper limit of normal (ULN); Hematocrit \<0.8×LLN, \>1.2×ULN; Red blood cells (RBC) count \<0.8×LLN, \>1.2×ULN; White blood cells (WBC) count \<0.5xLLN, \>1.5xULN; Platelet count \<75x10\^9/liter (L), \>600x10\^9/L; alanine aminotransferase (ALT) \>3xULN; aspartate aminotransferase (AST) \>3xULN; gamma-glutamyl transferase (GGT) \>3xULN; Alkaline phosphatase \>3xULN; Total bilirubin \>1.5xULN; Albumin \<25 grams per liter (g/L); Total protein \<0.8xLLN, \>1.2xULN; Creatinine \>1.5xULN; Blood urea nitrogen \>40 milligrams per deciliters (mg/dL); Sodium \<130 milliequivalents per liter (mEq/L), \>150 mEq/L; Potassium \<3.0 millimoles per liter (mmol/L), \>5.3 mmol/L; creatine phosphokinase (CPK) \>3xULN; Glucose \<50 mg/dL, \>300 mg/dL; Calcium \<7.7 mg/dL, \>11.1 mg/dL. Only categories with at least one participant with event are reported.
Time frame: Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8)
Population: Safety Analysis Set for the Active Drug Extension Period included all participants who were randomized and received at least 1 dose of study drug in the Active Drug Extension Period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | GGT: >3 x ULN | 0 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | Bilirubin: >1.5 x ULN | 0 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | ALT: >3 x ULN | 0 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | AST: >3 x ULN | 0 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | Potassium: >5.3 mmol/L | 0 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | Bilirubin: >1.5 x ULN | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | ALT: >3 x ULN | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | AST: >3 x ULN | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | GGT: >3 x ULN | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | Potassium: >5.3 mmol/L | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | Potassium: >5.3 mmol/L | 1 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | GGT: >3 x ULN | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | ALT: >3 x ULN | 2 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | Bilirubin: >1.5 x ULN | 1 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | AST: >3 x ULN | 2 Participants |
Primary
Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period
MAV criteria for ECG were: Heart rate \<40 bpm, \>115 bpm; PR interval ≤80 milliseconds (msec), ≥200 msec; QT interval with Fridericia correction method (QTcF) Interval ≤300 msec, \>500 msec or ≥30 msec change from baseline and \>450 msec; QRS duration ≤80 msec, ≥180 msec. Only categories with at least one participant with event are reported.
Time frame: Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8)
Population: Safety Analysis Set for the Active Drug Extension Period included all participants who were randomized and received at least 1 dose of study drug in the Active Drug Extension Period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period | PR Interval: ≥200 msec | 0 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period | Heart Rate: <40 bpm | 1 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period | QRS Duration: ≤80 msec | 3 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period | PR Interval: ≥200 msec | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period | Heart Rate: <40 bpm | 0 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period | QRS Duration: ≤80 msec | 3 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period | Heart Rate: <40 bpm | 1 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period | QRS Duration: ≤80 msec | 1 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period | PR Interval: ≥200 msec | 2 Participants |
Primary
Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period
MAV criteria for vital signs were: Pulse \<40 beats per minute (bpm), \>115 bpm; Systolic blood pressure \<90 millimeters of mercury (mmHg), ≥160 mmHg; Diastolic blood pressure \<50 mmHg, ≥100 mmHg, Systolic or Diastolic blood pressure change of \>20, \>30 mmHg from Baseline, Body temperature \>38.5 degree Celsius, Respiratory Rate \>21 breath/minute. Only categories with at least one participant with event are reported. Baseline for this outcome measure is Day 1 of the Active Drug Extension Period.
Time frame: Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8)
Population: Safety Analysis Set for the Active Drug Extension Period included all participants who were randomized and received at least 1 dose of study drug in the Active Drug Extension Period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Respiratory Rate: >21 breaths/minute | 1 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: Change from Pre-Dose >30 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Diastolic Blood Pressure: Change from Pre-Dose >30 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: <90 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Diastolic Blood Pressure: ≥100 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: Change from Pre-Dose >20 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: ≥160 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Diastolic Blood Pressure: Change from Pre-Dose >20 mmHg | 2 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: <90 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: ≥160 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Diastolic Blood Pressure: Change from Pre-Dose >30 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Respiratory Rate: >21 breaths/minute | 0 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: Change from Pre-Dose >20 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Diastolic Blood Pressure: Change from Pre-Dose >20 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: Change from Pre-Dose >30 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Diastolic Blood Pressure: ≥100 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Respiratory Rate: >21 breaths/minute | 2 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: <90 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: Change from Pre-Dose >20 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: Change from Pre-Dose >30 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Diastolic Blood Pressure: ≥100 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Diastolic Blood Pressure: Change from Pre-Dose >20 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Diastolic Blood Pressure: Change from Pre-Dose >30 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | Systolic Blood Pressure: ≥160 mmHg | 0 Participants |
Primary
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) During the Active Drug Extension Period
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participants administered a drug; it does not necessarily have to have a causal relationship with this treatment. 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 is defined as an AE with an onset that occurs after receiving study drug.
Time frame: Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8)
Population: Safety Analysis Set for the Active Drug Extension Period included all participants who were randomized and received at least 1 dose of study drug in the Active Drug Extension Period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) During the Active Drug Extension Period | 5 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) During the Active Drug Extension Period | 4 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) During the Active Drug Extension Period | 3 Participants |
Secondary
Number of Participants With at Least One Post-dose MAV for ECG Parameters During the Double-blind Randomized Withdrawal Period
MAV criteria for ECG were: Heart rate \<40 bpm, \>115 bpm; PR interval ≤80 msec, ≥200 msec; QTcF Interval ≤300 msec, \>500 msec or ≥30 msec change from baseline and \>450 msec; QRS duration ≤80 msec, ≥180 msec. Only categories with at least one participant with event are reported.
Time frame: Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12)
Population: Safety Analysis Set for the Double-blind Randomized Withdrawal Period included all participants who were randomized and received at least 1 dose of study drug in the Double-blind Randomized Withdrawal Period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for ECG Parameters During the Double-blind Randomized Withdrawal Period | 0 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for ECG Parameters During the Double-blind Randomized Withdrawal Period | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for ECG Parameters During the Double-blind Randomized Withdrawal Period | 0 Participants |
| Double-blind Randomized Withdrawal Period: Placebo | Number of Participants With at Least One Post-dose MAV for ECG Parameters During the Double-blind Randomized Withdrawal Period | 1 Participants |
Secondary
Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period
MAV criteria for vital signs were: Pulse \<40 bpm, \>115 bpm; Systolic blood pressure \<90 mmHg, ≥160 mmHg; Diastolic blood pressure \<50 mmHg, ≥100 mmHg, Systolic or Diastolic blood pressure change of \>20, \>30 mmHg from Baseline, Body temperature \>38.5 degree Celsius, Respiratory Rate \>21 breath/minute. Only categories with at least one participant with event are reported. Baseline for this outcome measure is Day 1 of the Double-blind Randomized Withdrawal Period (Day 57 of this study).
Time frame: Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12)
Population: Safety Analysis Set for the Double-blind Randomized Withdrawal Period included all participants who were randomized and received at least 1 dose of study drug in the Double-blind Randomized Withdrawal Period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Systolic Blood Pressure: <90 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Diastolic Blood Pressure: Change from Baseline >20 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Systolic Blood Pressure: Change from Baseline >20 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Systolic Blood Pressure: <90 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Diastolic Blood Pressure: Change from Baseline >20 mmHg | 1 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Systolic Blood Pressure: Change from Baseline >20 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Systolic Blood Pressure: Change from Baseline >20 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Systolic Blood Pressure: <90 mmHg | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Diastolic Blood Pressure: Change from Baseline >20 mmHg | 0 Participants |
| Double-blind Randomized Withdrawal Period: Placebo | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Systolic Blood Pressure: <90 mmHg | 1 Participants |
| Double-blind Randomized Withdrawal Period: Placebo | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Diastolic Blood Pressure: Change from Baseline >20 mmHg | 1 Participants |
| Double-blind Randomized Withdrawal Period: Placebo | Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | Systolic Blood Pressure: Change from Baseline >20 mmHg | 0 Participants |
Secondary
Number of Participants With at Least One Post-dose MAV in Laboratory Test During the Double-blind Randomized Withdrawal Period
Clinical laboratory tests included hematology, serum chemistry, and urinalysis. MAV criteria: Hemoglobin \<0.8×LLN, \>1.2×ULN; Hematocrit \<0.8×LLN, \>1.2×ULN; RBC count \<0.8×LLN, \>1.2×ULN; WBC count \<0.5xLLN, \>1.5xULN; Platelet count \<75x10\^9/L, \>600x10\^9/L; ALT \>3xULN; AST \>3xULN; GGT \>3xULN; Alkaline phosphatase \>3xULN; Total bilirubin \>1.5xULN; Albumin \<25 g/L; Total protein \<0.8x LLN, \>1.2xULN; Creatinine \>1.5xULN; Blood urea nitrogen \>40 mg/dL; Sodium \<130 mEq/L, \>150 mEq/L; Potassium \<3.0 mmol/L, \>5.3 mmol/L; CPK \>3xULN; Glucose \<50 mg/dL, \>300 mg/dL; Calcium \<7.7 mg/dL, \>11.1 mg/dL.
Time frame: Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12)
Population: Safety Analysis Set for the Double-blind Randomized Withdrawal Period included all participants who were randomized and received at least 1 dose of study drug in the Double-blind Randomized Withdrawal Period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One Post-dose MAV in Laboratory Test During the Double-blind Randomized Withdrawal Period | 0 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One Post-dose MAV in Laboratory Test During the Double-blind Randomized Withdrawal Period | 0 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One Post-dose MAV in Laboratory Test During the Double-blind Randomized Withdrawal Period | 0 Participants |
| Double-blind Randomized Withdrawal Period: Placebo | Number of Participants With at Least One Post-dose MAV in Laboratory Test During the Double-blind Randomized Withdrawal Period | 0 Participants |
Secondary
Number of Participants With at Least One TEAE During the Double-blind Randomized Withdrawal Period
An AE is defined as any untoward medical occurrence in a clinical investigation participants administered a drug; it does not necessarily have to have a causal relationship with this treatment. 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 is defined as an AE with an onset that occurs after receiving study drug.
Time frame: Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12)
Population: Safety Analysis Set for the Double-blind Randomized Withdrawal Period included all participants who were randomized and received at least 1 dose of study drug in the Double-blind Randomized Withdrawal Period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Drug Extension Period: TAK-994 30 mg | Number of Participants With at Least One TEAE During the Double-blind Randomized Withdrawal Period | 0 Participants |
| Active Drug Extension Period: TAK-994 90 mg | Number of Participants With at Least One TEAE During the Double-blind Randomized Withdrawal Period | 1 Participants |
| Active Drug Extension Period: TAK-994 180 mg | Number of Participants With at Least One TEAE During the Double-blind Randomized Withdrawal Period | 0 Participants |
| Double-blind Randomized Withdrawal Period: Placebo | Number of Participants With at Least One TEAE During the Double-blind Randomized Withdrawal Period | 1 Participants |