Trial Outcomes & Findings for A Phase 2 Efficacy and Safety Study of TAK-063 in Participants With an Acute Exacerbation of Schizophrenia (NCT NCT02477020)

NCT ID: NCT02477020

Last Updated: 2017-09-29

Results Overview

PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210; higher score indicates greater severity. Least square mean and standard error values were determined using a mixed model for repeated measures (MMRM). A negative change from Baseline indicates improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 164 participants
• Primary outcome timeframe: Baseline and Week 6
• Results posted on: 2017-09-29

Participant Flow

Participants took part in the study at 13 investigative sites in United States from 01 July 2015 to 27 July 2016.

Participants with a diagnosis of acute exacerbation of schizophrenia were enrolled in two treatment groups TAK-063 or placebo.

Participant milestones

Measure	Placebo TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Overall Study STARTED	81	83
Overall Study COMPLETED	51	55
Overall Study NOT COMPLETED	30	28

Reasons for withdrawal

Measure	Placebo TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Overall Study Pretreatment Event/Adverse Event	6	6
Overall Study Voluntary Withdrawal	7	16
Overall Study Reason not Specified	3	1
Overall Study Lack of Efficacy	14	5

Baseline Characteristics

A Phase 2 Efficacy and Safety Study of TAK-063 in Participants With an Acute Exacerbation of Schizophrenia

Baseline characteristics by cohort

Measure	Placebo n=81 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=83 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.	Total n=164 Participants Total of all reporting groups
Age, Continuous	41.2 years STANDARD_DEVIATION 10.44 • n=5 Participants	42.3 years STANDARD_DEVIATION 10.36 • n=7 Participants	41.8 years STANDARD_DEVIATION 10.38 • n=5 Participants
Age, Customized 18 - 50 years	62 participants n=5 Participants	57 participants n=7 Participants	119 participants n=5 Participants
Age, Customized 51 - 65 years	19 participants n=5 Participants	26 participants n=7 Participants	45 participants n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	18 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	67 Participants n=5 Participants	65 Participants n=7 Participants	132 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	14 participants n=5 Participants	6 participants n=7 Participants	20 participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic and Latino	67 participants n=5 Participants	77 participants n=7 Participants	144 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	43 participants n=5 Participants	65 participants n=7 Participants	108 participants n=5 Participants
Race/Ethnicity, Customized White	33 participants n=5 Participants	16 participants n=7 Participants	49 participants n=5 Participants
Race/Ethnicity, Customized Multiracial	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment United States	81 participants n=5 Participants	83 participants n=7 Participants	164 participants n=5 Participants
Height	176.1 cm STANDARD_DEVIATION 9.02 • n=5 Participants	174.3 cm STANDARD_DEVIATION 9.41 • n=7 Participants	175.2 cm STANDARD_DEVIATION 9.23 • n=5 Participants
Weight	86.64 kg STANDARD_DEVIATION 16.490 • n=5 Participants	82.46 kg STANDARD_DEVIATION 15.480 • n=7 Participants	84.52 kg STANDARD_DEVIATION 16.075 • n=5 Participants
Body Mass Index (BMI)	27.84 kg/m^2 STANDARD_DEVIATION 4.427 • n=5 Participants	27.17 kg/m^2 STANDARD_DEVIATION 4.231 • n=7 Participants	27.50 kg/m^2 STANDARD_DEVIATION 4.329 • n=5 Participants
Smoking Classification Has never smoked	7 participants n=5 Participants	7 participants n=7 Participants	14 participants n=5 Participants
Smoking Classification Is a current smoker	67 participants n=5 Participants	73 participants n=7 Participants	140 participants n=5 Participants
Smoking Classification Is an ex-smoker	7 participants n=5 Participants	3 participants n=7 Participants	10 participants n=5 Participants
Alcohol Classification Has never drunk	27 participants n=5 Participants	21 participants n=7 Participants	48 participants n=5 Participants
Alcohol Classification Is a current drinker	21 participants n=5 Participants	31 participants n=7 Participants	52 participants n=5 Participants
Alcohol Classification Is an ex-drinker	33 participants n=5 Participants	31 participants n=7 Participants	64 participants n=5 Participants
Consume Caffeine Yes	73 participants n=5 Participants	74 participants n=7 Participants	147 participants n=5 Participants
Consume Caffeine No	8 participants n=5 Participants	9 participants n=7 Participants	17 participants n=5 Participants
Female Reproductive Status Postmenopausal	7 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants
Female Reproductive Status Surgically Sterile	1 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants
Female Reproductive Status Female of Childbearing Potential	6 participants n=5 Participants	8 participants n=7 Participants	14 participants n=5 Participants
Female Reproductive Status Not applicable (Male participant)	67 participants n=5 Participants	65 participants n=7 Participants	132 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here number of participants analyzed are participants evaluable for this outcome measure.

PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210; higher score indicates greater severity. Least square mean and standard error values were determined using a mixed model for repeated measures (MMRM). A negative change from Baseline indicates improvement.

Outcome measures

Measure	Placebo n=51 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=55 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the Positive and Negative Symptom Scale (PANSS) Total Score at Week 6	-14.08 score on a scale Standard Error 2.474	-19.54 score on a scale Standard Error 2.412

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 3, 4 and 5

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here 'n' refers to number of participants analyzed at each time point.

PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210; higher score indicates greater severity. Least square mean and standard error values were determined using a MMRM. A negative change from Baseline indicates improvement.

Outcome measures

Measure	Placebo n=76 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=80 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in PANSS Total Score at Weeks 1, 2, 3, 4 and 5 Change at Week 2 (n = 72, 72)	-9.73 score on a scale Standard Error 1.604	-11.95 score on a scale Standard Error 1.580
Change From Baseline in PANSS Total Score at Weeks 1, 2, 3, 4 and 5 Change at Week 3 (n = 67, 68)	-10.91 score on a scale Standard Error 2.017	-14.37 score on a scale Standard Error 1.985
Change From Baseline in PANSS Total Score at Weeks 1, 2, 3, 4 and 5 Change at Week 4 (n = 57, 60)	-12.80 score on a scale Standard Error 2.256	-14.91 score on a scale Standard Error 2.212
Change From Baseline in PANSS Total Score at Weeks 1, 2, 3, 4 and 5 Change at Week 5 (n = 53, 58)	-13.03 score on a scale Standard Error 2.321	-16.94 score on a scale Standard Error 2.268
Change From Baseline in PANSS Total Score at Weeks 1, 2, 3, 4 and 5 Change at Week 1 (n = 76, 80)	-8.30 score on a scale Standard Error 1.106	-9.09 score on a scale Standard Error 1.075

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 3, 4, 5 and 6

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here 'n' refers to number of participants analyzed at each time point.

PANSS subscales using the Marder 5-factor model include positive symptoms (8-items, total score = total score = 8 to 56, with a higher score indicating greater severity of symptoms), negative symptoms (7-items, total score = 7 to 49, with a higher score indicating greater severity of symptoms), disorganized thoughts (7-items, total score = 7 to 49, with a higher score indicating greater severity of symptoms), impulsivity/hostility (4-items, total score = 4 to 28, with a higher score indicating greater severity of symptoms), anxiety/depression (4-items, total score = 4 to 28, with a higher score indicating greater severity of symptoms). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. An improvement in symptoms is represented by change from baseline values that are negative.

Outcome measures

Measure	Placebo n=76 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=80 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Negative symptoms, Change at Week 1 (n=76,80)	-1.67 score on a scale Standard Error 0.415	-1.33 score on a scale Standard Error 0.405
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Negative symptoms, Change at Week 2 (n=72,72)	-1.88 score on a scale Standard Error 0.545	-2.49 score on a scale Standard Error 0.538
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Negative symptoms, Change at Week 3 (n=67,68)	-2.87 score on a scale Standard Error 0.589	-2.72 score on a scale Standard Error 0.580
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Negative symptoms, Change at Week 4 (n=57,60)	-2.64 score on a scale Standard Error 0.673	-3.23 score on a scale Standard Error 0.661
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Negative symptoms, Change at Week 5 (n=53,58)	-3.01 score on a scale Standard Error 0.679	-3.15 score on a scale Standard Error 0.662
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Disorganized thoughts, Change at Week 1 (n=76,80)	-1.04 score on a scale Standard Error 0.298	-1.41 score on a scale Standard Error 0.290
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Disorganized thoughts, Change at Week 2 (n=72,72)	-1.55 score on a scale Standard Error 0.382	-1.77 score on a scale Standard Error 0.377
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Disorganized thoughts, Change at Week 4 (n=57,60)	-1.92 score on a scale Standard Error 0.505	-1.92 score on a scale Standard Error 0.497
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Disorganized thoughts, Change at Week 5 (n=53,58)	-1.37 score on a scale Standard Error 0.562	-2.10 score on a scale Standard Error 0.550
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Disorganized thoughts, Change at Week 6 (n=51,55)	-1.90 score on a scale Standard Error 0.579	-3.16 score on a scale Standard Error 0.565
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Hostility, Change at Week 1 (n=76,80)	-1.32 score on a scale Standard Error 0.342	-1.64 score on a scale Standard Error 0.334
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Hostility, Change at Week 2 (n=72,72)	-1.40 score on a scale Standard Error 0.364	-1.36 score on a scale Standard Error 0.360
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Hostility, Change at Week 3 (n=67,68)	-0.83 score on a scale Standard Error 0.434	-1.70 score on a scale Standard Error 0.430
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Hostility, Change at Week 4 (n=57,60)	-1.21 score on a scale Standard Error 0.492	-1.21 score on a scale Standard Error 0.482
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Hostility, Change at Week 5 (n=53,58)	-1.43 score on a scale Standard Error 0.494	-2.04 score on a scale Standard Error 0.478
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Anxiety, Change at Week 1 (n=76,80)	-2.11 score on a scale Standard Error 0.290	-1.86 score on a scale Standard Error 0.284
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Anxiety, Change at Week 3 (n=67,68)	-2.70 score on a scale Standard Error 0.376	-3.19 score on a scale Standard Error 0.373
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Anxiety, Change at Week 4 (n=57,60)	-3.42 score on a scale Standard Error 0.427	-3.74 score on a scale Standard Error 0.419
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Positive symptoms, Change at Week 5 (n=53,58)	-4.65 score on a scale Standard Error 0.779	-6.67 score on a scale Standard Error 0.760
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Positive symptoms, Change at Week 1 (n=76,80)	-2.64 score on a scale Standard Error 0.410	-3.37 score on a scale Standard Error 0.397
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Positive symptoms, Change at Week 2 (n=72,72)	-3.20 score on a scale Standard Error 0.561	-4.39 score on a scale Standard Error 0.554
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Positive symptoms, Change at Week 6 (n=51,55)	-5.33 score on a scale Standard Error 0.800	-7.23 score on a scale Standard Error 0.778
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Positive symptoms, Change at Week 3 (n=67,68)	-3.67 score on a scale Standard Error 0.683	-5.61 score on a scale Standard Error 0.674
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Positive symptoms, Change at Week 4 (n=57,60)	-4.49 score on a scale Standard Error 0.731	-6.03 score on a scale Standard Error 0.717
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Negative symptoms, Change at Week 6 (n=51,55)	-3.38 score on a scale Standard Error 0.681	-4.11 score on a scale Standard Error 0.662
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Disorganized thoughts, Change at Week 3 (n=67,68)	-1.60 score on a scale Standard Error 0.444	-2.06 score on a scale Standard Error 0.439
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Hostility, Change at Week 6 (n=51,55)	-1.16 score on a scale Standard Error 0.476	-2.28 score on a scale Standard Error 0.462
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Anxiety, Change at Week 2 (n=72,72)	-2.29 score on a scale Standard Error 0.361	-2.70 score on a scale Standard Error 0.359
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Anxiety, Change at Week 5 (n=53,58)	-3.80 score on a scale Standard Error 0.414	-4.32 score on a scale Standard Error 0.402
Change From Baseline in PANSS Subscales Using the Marder 5-factor Model at Weeks 1, 2, 3, 4, 5, and 6 Anxiety, Change at Week 6 (n=51,55)	-3.66 score on a scale Standard Error 0.460	-4.34 score on a scale Standard Error 0.447

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 3, 4, 5 and 6

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here 'n' refers to number of participants analyzed at each time point.

PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Positive subscale consists of 7 items which assesses the positive symptoms with subscale score ranging from 7 to 49, where higher score indicates greater severity. Negative subscale consists of 7 items which assesses the negative symptoms with subscale score ranging from 7 to 49, where higher score indicates greater severity. General psychopathology subscale consists of 16 items which assesses the general symptoms of schizophrenia with subscale score ranging from 16 to 96, where higher score indicates greater severity. Least square mean and standard error values were determined using a MMRM. A negative change from Baseline indicates improvement.

Outcome measures

Measure	Placebo n=76 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=80 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Positive Score, Change at Week 1 (n=76,80)	-2.80 score on a scale Standard Error 0.434	-3.49 score on a scale Standard Error 0.420
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Positive Score, Change at Week 2 (n=72,72)	-3.63 score on a scale Standard Error 0.566	-4.35 score on a scale Standard Error 0.556
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Positive Score, Change at Week 3 (n=67,68)	-3.87 score on a scale Standard Error 0.677	-5.35 score on a scale Standard Error 0.666
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Positive Score, Change at Week 4 (n=57,60)	-4.42 score on a scale Standard Error 0.729	-5.62 score on a scale Standard Error 0.715
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Positive Score, Change at Week 5 (n=53,58)	-4.61 score on a scale Standard Error 0.757	-6.33 score on a scale Standard Error 0.738
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Positive Score, Change at Week 6 (n=51,55)	-5.35 score on a scale Standard Error 0.789	-6.95 score on a scale Standard Error 0.767
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Negative Score, Change at Week 1 (n=76,80)	-1.30 score on a scale Standard Error 0.369	-1.24 score on a scale Standard Error 0.360
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Negative Score, Change at Week 2 (n=72,72)	-1.12 score on a scale Standard Error 0.498	-1.71 score on a scale Standard Error 0.493
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Negative Score, Change at Week 3 (n=67,68)	-1.77 score on a scale Standard Error 0.519	-2.14 score on a scale Standard Error 0.513
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Negative Score, Change at Week 4 (n=57,60)	-1.98 score on a scale Standard Error 0.615	-2.35 score on a scale Standard Error 0.604
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Negative Score, Change at Week 5 (n=53,58)	-2.14 score on a scale Standard Error 0.644	-2.36 score on a scale Standard Error 0.627
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS Negative Score, Change at Week 6 (n=51,55)	-2.29 score on a scale Standard Error 0.617	-3.44 score on a scale Standard Error 0.599
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS General Score, Change at Week 1 (n=76,80)	-4.54 score on a scale Standard Error 0.587	-4.47 score on a scale Standard Error 0.573
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS General Score, Change at Week 2 (n=72,72)	-5.43 score on a scale Standard Error 0.828	-6.05 score on a scale Standard Error 0.819
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS General Score, Change at Week 3 (n=67,68)	-5.85 score on a scale Standard Error 1.043	-7.15 score on a scale Standard Error 1.029
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS General Score, Change at Week 4 (n=57,60)	-6.96 score on a scale Standard Error 1.165	-7.33 score on a scale Standard Error 1.146
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS General Score, Change at Week 5 (n=53,58)	-7.12 score on a scale Standard Error 1.166	-8.73 score on a scale Standard Error 1.140
Change From Baseline in PANSS Subscales at Weeks 1, 2, 3, 4, 5 and 6 PANSS General Score, Change at Week 6 (n=51,55)	-7.35 score on a scale Standard Error 1.245	-9.79 score on a scale Standard Error 1.217

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 5 and 6

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here 'n' refers to number of participants analyzed at each time point.

Clinical responders based on the PANSS total score is defined as at least 30% improvement from baseline in the total score. PANSS assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). The sum of the 30 items is defined as the PANSS total score and ranges from 30 to 210; higher score indicates greater severity.

Outcome measures

Measure	Placebo n=76 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=80 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Percentage of Clinical Responders Based on the PANSS Total Score Week 1 (n=76,80)	6.6 percentage of participants	20.0 percentage of participants
Percentage of Clinical Responders Based on the PANSS Total Score Week 2 (n=72,72)	18.1 percentage of participants	37.5 percentage of participants
Percentage of Clinical Responders Based on the PANSS Total Score Week 3 (n=67,68)	26.9 percentage of participants	39.7 percentage of participants
Percentage of Clinical Responders Based on the PANSS Total Score Week 4 (n=57,60)	38.6 percentage of participants	43.3 percentage of participants
Percentage of Clinical Responders Based on the PANSS Total Score Week 5 (n=53,58)	37.7 percentage of participants	48.3 percentage of participants
Percentage of Clinical Responders Based on the PANSS Total Score Week 6 (n=51,55)	43.1 percentage of participants	54.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 3, 4, 5 and 6

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here 'n' refers to number of participants analyzed at each time point.

The CGI-S is a clinician rated scale designed to assess global severity of illness. CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment. A participant is assessed on severity of mental illness on the following scale: 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. Least square mean and standard error values were determined using a MMRM. A negative change from Baseline indicates improvement.

Outcome measures

Measure	Placebo n=76 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=80 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Weeks 1, 2, 3, 4, 5,and 6 Change at Week 1 (n=76,80)	-0.39 score on a scale Standard Error 0.069	-0.44 score on a scale Standard Error 0.067
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Weeks 1, 2, 3, 4, 5,and 6 Change at Week 2 (n=72,72)	-0.45 score on a scale Standard Error 0.097	-0.67 score on a scale Standard Error 0.096
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Weeks 1, 2, 3, 4, 5,and 6 Change at Week 3 (n=68,68)	-0.55 score on a scale Standard Error 0.118	-0.99 score on a scale Standard Error 0.118
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Weeks 1, 2, 3, 4, 5,and 6 Change at Week 4 (n=57,60)	-0.58 score on a scale Standard Error 0.129	-0.94 score on a scale Standard Error 0.127
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Weeks 1, 2, 3, 4, 5,and 6 Change at Week 5 (n=53,58)	-0.66 score on a scale Standard Error 0.137	-1.13 score on a scale Standard Error 0.134
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Weeks 1, 2, 3, 4, 5,and 6 Change at Week 6 (n=51,55)	-0.76 score on a scale Standard Error 0.145	-1.19 score on a scale Standard Error 0.141

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 5 and 6

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here 'n' refers to number of participants analyzed at each time point.

The CGI-I assesses the participant's improvement (or worsening). The clinician is required to assess the participant's condition relative to baseline on a 7-point scale. CGI-I scale assesses the participant's improvement (or worsening) on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Least square mean and standard error values were calculated using a MMRM.

Outcome measures

Measure	Placebo n=76 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=80 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Clinical Global Impression Scale - Improvement (CGI-I) Score at Weeks 1, 2, 3, 4, 5 and 6 Week 1 (n=76,80)	3.53 score on a scale Standard Error 0.093	3.49 score on a scale Standard Error 0.091
Clinical Global Impression Scale - Improvement (CGI-I) Score at Weeks 1, 2, 3, 4, 5 and 6 Week 2 (n=72,72)	3.58 score on a scale Standard Error 0.124	3.20 score on a scale Standard Error 0.123
Clinical Global Impression Scale - Improvement (CGI-I) Score at Weeks 1, 2, 3, 4, 5 and 6 Week 3 (n=67,68)	3.63 score on a scale Standard Error 0.144	3.07 score on a scale Standard Error 0.144
Clinical Global Impression Scale - Improvement (CGI-I) Score at Weeks 1, 2, 3, 4, 5 and 6 Week 4 (n=57,60)	3.53 score on a scale Standard Error 0.157	2.97 score on a scale Standard Error 0.155
Clinical Global Impression Scale - Improvement (CGI-I) Score at Weeks 1, 2, 3, 4, 5 and 6 Week 5 (n=53,58)	3.54 score on a scale Standard Error 0.171	2.98 score on a scale Standard Error 0.167
Clinical Global Impression Scale - Improvement (CGI-I) Score at Weeks 1, 2, 3, 4, 5 and 6 Week 6 (n=51,55)	3.46 score on a scale Standard Error 0.175	2.80 score on a scale Standard Error 0.171

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 5 and 6

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here 'n' refers to number of participants analyzed at each time point.

Responder based on CGI-I is defined as a rating of much improved or very much improved. The CGI-I assesses the participant's improvement (or worsening). The clinician is required to assess the participant's condition relative to baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.

Outcome measures

Measure	Placebo n=76 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=80 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Percentage of Responders Based on CGI-I Ratings Score Week 1 (n=76,80)	6.6 percentage of participants	15.0 percentage of participants
Percentage of Responders Based on CGI-I Ratings Score Week 2 (n=72,72)	18.1 percentage of participants	31.9 percentage of participants
Percentage of Responders Based on CGI-I Ratings Score Week 3 (n=67,68)	19.4 percentage of participants	36.8 percentage of participants
Percentage of Responders Based on CGI-I Ratings Score Week 4 (n=57,60)	31.6 percentage of participants	43.3 percentage of participants
Percentage of Responders Based on CGI-I Ratings Score Week 5 (n=53,58)	32.1 percentage of participants	44.8 percentage of participants
Percentage of Responders Based on CGI-I Ratings Score Week 6 (n=51,55)	29.4 percentage of participants	58.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here 'n' refers to number of participants analyzed at each time point.

BACS is specifically designed to measure treatment- related improvements in cognition and includes alternate forms. The battery of tests in the BACS includes brief assessments of reasoning and problem solving, verbal fluency, attention, verbal memory, working memory, and motor speed. The primary measure from each test of the BACS is standardized by creating z-scores whereby the mean of the test session of a healthy participant is set to 0 and the standard deviation set to 1. A composite score was calculated by averaging all of the 6 standardized primary measures from the BACS, and then calculating a z-score of the composite. The composite z-score indicates how much higher or lower the participant's cognition is compared to a healthy person. Least square mean and standard error values were determined using a MMRM.

Outcome measures

Measure	Placebo n=76 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=80 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Brief Assessment of Cognition in Schizophrenia (BACS) Score at Weeks 3 and 6 Change at Week 3 (n=69,71)	0.69 z-score Standard Error 1.120	2.49 z-score Standard Error 1.104
Change From Baseline in Brief Assessment of Cognition in Schizophrenia (BACS) Score at Weeks 3 and 6 Change at Week 6 (n=49,54)	2.33 z-score Standard Error 1.290	4.52 z-score Standard Error 1.251

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here 'n' refers to number of participants analyzed at each time point.

The BNSS is a13-item instrument designed for use in clinical trials and other studies that measures 5 domains of negative symptoms: blunted affect, alogia, asociality, anhedonia, and avolition. All the items in the BNSS are rated on a 7-point (0-6) scale, with anchor points generally ranging from the symptom's being absent (0) to severe (6). A scale total score is calculated by summing the 13 individual items; total score range of 0 to 78, where higher score indicates higher severity of negative symptoms. Least square mean and standard error values were determined using a MMRM. A negative change from Baseline indicates improvement.

Outcome measures

Measure	Placebo n=76 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=80 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in Brief Negative Symptom Scale (BNSS) Score at Weeks 3 and 6 Change at Week 3 (n=71,75)	-3.70 score on a scale Standard Error 1.217	-4.08 score on a scale Standard Error 1.185
Change From Baseline in Brief Negative Symptom Scale (BNSS) Score at Weeks 3 and 6 Change at Week 6 (n=51,55)	-4.93 score on a scale Standard Error 1.498	-7.80 score on a scale Standard Error 1.451

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here 'n' refers to number of participants analyzed at each time point.

The PSP scale is a clinician-reported outcome instrument that was developed to evaluate social and personal functioning. It measures 4 domains of social functioning: socially useful activities including work and study, personal and social relationships, self-care and disturbing and aggressive behaviors. The clinician assigns an initial 6-degree of severity to each area (absent, mild, manifest, marked, severe or very severe). The final result is a single assessment of social functioning ranging from 0 (no autonomy) to 100 (excellent functioning). Least square mean and standard error values were determined using a MMRM. A positive change from Baseline indicates improvement.

Outcome measures

Measure	Placebo n=76 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=80 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the Personal and Social Performance (PSP) Scale Score at Weeks 3 and 6 Change at Week 3 (n=70,75)	7.19 score on a scale Standard Error 1.301	9.88 score on a scale Standard Error 1.244
Change From Baseline in the Personal and Social Performance (PSP) Scale Score at Weeks 3 and 6 Change at Week 6 (n=50,55)	9.65 score on a scale Standard Error 1.693	12.27 score on a scale Standard Error 1.605

SECONDARY outcome

Timeframe: Baseline, Weeks 3 and 6

Population: The full analysis set included all participants who were randomized, received at least one dose of study drug and have a baseline value and at least one valid postbaseline value for assessment of primary efficacy. Here 'n' refers to number of participants analyzed at each time point.

The UPSA-B evaluates the abilities of individuals to perform everyday tasks that are considered necessary for independent functioning in the community. The UPSA-B uses role playing situations to evaluate skills in 5 areas: household chores, communication, finance, transportation, and planning recreational activities. Subscale scores range from 0 to 20 points, and total scores range from 0 to 100 points; higher scores reflect better performance. Least square mean and standard error values were determined using a MMRM. A positive change from Baseline indicates improvement.

Outcome measures

Measure	Placebo n=76 Participants TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=80 Participants TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Change From Baseline in the University of California San Diego Performance-based Skills Assessment - Brief Version (UPSA-B) at Week 3 and 6 Change at Week 3 (n=69,71)	2.13 score on a scale Standard Error 1.337	2.20 score on a scale Standard Error 1.322
Change From Baseline in the University of California San Diego Performance-based Skills Assessment - Brief Version (UPSA-B) at Week 3 and 6 Change at Week 6 (n=49,54)	3.97 score on a scale Standard Error 1.656	3.43 score on a scale Standard Error 1.592

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 42 other events

Deaths: 0 deaths

TAK-063

Serious events: 4 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=81 participants at risk TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=83 participants at risk TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Infections and infestations Cellulitis	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Agitation	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.2% 1/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Schizophrenia	0.00% 0/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Suicidal ideation	0.00% 0/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.2% 1/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Measure	Placebo n=81 participants at risk TAK-063 matching-placebo tablets, orally, once daily for up to 6 weeks.	TAK-063 n=83 participants at risk TAK-063 20 mg, tablets, orally, once daily for up to 6 weeks.
Gastrointestinal disorders Dry mouth	3.7% 3/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Dyspepsia	7.4% 6/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	10.8% 9/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	6.2% 5/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.0% 5/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	7.4% 6/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.6% 3/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Neck pain	7.4% 6/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.2% 1/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Akathisia	4.9% 4/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.3% 11/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Headache	11.1% 9/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.2% 6/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Somnolence	2.5% 2/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.0% 10/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhoea	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.6% 3/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dystonia	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.0% 5/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Decreased appetite	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.0% 5/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Toothache	2.5% 2/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.8% 4/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Vomiting	2.5% 2/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.8% 4/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal discomfort	3.7% 3/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain upper	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pain	2.5% 2/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.2% 1/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nasopharyngitis	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Tooth abscess	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Upper respiratory tract infection	2.5% 2/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.6% 3/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Weight increased	3.7% 3/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Increased appetite	2.5% 2/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	4.9% 4/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.8% 4/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	3.7% 3/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Back pain	2.5% 2/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Torticollis	0.00% 0/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Trismus	0.00% 0/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	3.7% 3/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.2% 1/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Paraesthesia	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Tremor	2.5% 2/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.2% 1/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Anxiety	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.6% 3/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Insomnia	3.7% 3/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Psychotic disorder	1.2% 1/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Agitation	2.5% 2/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.7% 3/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.6% 3/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	4.9% 4/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.2% 1/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hot flush	0.00% 0/81 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.4% 2/83 • Up to 14 days after the last dose (Up to Week 8) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER