Trial Outcomes & Findings for Biomarker Qualification for Risk of Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease (AD) and Safety and Efficacy Evaluation of Pioglitazone in Delaying Its Onset (NCT NCT01931566)

NCT ID: NCT01931566

Last Updated: 2019-09-16

Results Overview

The event definition for MCI-AD was the time in days from the randomization date to the date of the first of two consecutive scheduled visits at which a participant was assessed with a diagnosis of MCI due to AD confirmed by adjudication committee. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to the largest event time.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

3494 participants

Primary outcome timeframe

Baseline to the end of study (approximately up to 5 years)

Results posted on

2019-09-16

Participant Flow

Participants took part in the study at 57 investigative sites in United States, United Kingdom, Germany, Australia, and Switzerland from 01 Aug 2013 to 06 Sep 2018.

Participants at least 65 years old with normal cognitive function were enrolled to receive either pioglitazone (0.8 mg sustained release tablet) or placebo.

Participant milestones

Participant milestones
Measure	Low Risk Placebo Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to low risk group for developing MCI-AD for up to 5 years.	High Risk Placebo Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.	High Risk Pioglitazone Pioglitazone 0.8 mg, sustained release (SR) tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.
Overall Study STARTED	433	1516	1545
Overall Study Treated	427	1507	1531
Overall Study COMPLETED	4	40	39
Overall Study NOT COMPLETED	429	1476	1506

Reasons for withdrawal

Reasons for withdrawal
Measure	Low Risk Placebo Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to low risk group for developing MCI-AD for up to 5 years.	High Risk Placebo Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.	High Risk Pioglitazone Pioglitazone 0.8 mg, sustained release (SR) tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.
Overall Study Randomized But Not Treated	6	9	14
Overall Study Adverse Event	37	167	132
Overall Study Major Protocol Deviation	5	14	21
Overall Study Lost to Follow-up	3	26	23
Overall Study Voluntary Withdrawal	78	245	225
Overall Study Study Termination	289	968	1037
Overall Study Reason Not Specified	11	47	53
Overall Study Missing	0	0	1

Baseline Characteristics

Biomarker Qualification for Risk of Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease (AD) and Safety and Efficacy Evaluation of Pioglitazone in Delaying Its Onset

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Risk Placebo n=433 Participants Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to low risk group for developing MCI-AD for up to 5 years.	High Risk Placebo n=1516 Participants Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.	High Risk Pioglitazone n=1545 Participants Pioglitazone 0.8 mg, sustained release (SR) tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.	Total n=3494 Participants Total of all reporting groups
Age, Continuous	70.3 years STANDARD_DEVIATION 4.02 • n=5 Participants	74.6 years STANDARD_DEVIATION 5.27 • n=7 Participants	74.4 years STANDARD_DEVIATION 5.25 • n=5 Participants	74.0 years STANDARD_DEVIATION 5.31 • n=4 Participants
Age, Customized <75 years	360 Participants n=5 Participants	632 Participants n=7 Participants	658 Participants n=5 Participants	1650 Participants n=4 Participants
Age, Customized >=75 years	73 Participants n=5 Participants	884 Participants n=7 Participants	887 Participants n=5 Participants	1844 Participants n=4 Participants
Sex: Female, Male Female	259 Participants n=5 Participants	850 Participants n=7 Participants	812 Participants n=5 Participants	1921 Participants n=4 Participants
Sex: Female, Male Male	174 Participants n=5 Participants	666 Participants n=7 Participants	733 Participants n=5 Participants	1573 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	19 Participants n=7 Participants	12 Participants n=5 Participants	39 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	425 Participants n=5 Participants	1497 Participants n=7 Participants	1533 Participants n=5 Participants	3455 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	10 Participants n=7 Participants	14 Participants n=5 Participants	25 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	10 Participants n=5 Participants	38 Participants n=7 Participants	39 Participants n=5 Participants	87 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White	421 Participants n=5 Participants	1463 Participants n=7 Participants	1484 Participants n=5 Participants	3368 Participants n=4 Participants
Race/Ethnicity, Customized Multiracial	1 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Non-Hispanic/Latino Caucasian	413 Participants n=5 Participants	1444 Participants n=7 Participants	1472 Participants n=5 Participants	3329 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic/Latino and/or non-Caucasian	20 Participants n=5 Participants	72 Participants n=7 Participants	73 Participants n=5 Participants	165 Participants n=4 Participants
Region of Enrollment United States	270 Participants n=5 Participants	962 Participants n=7 Participants	985 Participants n=5 Participants	2217 Participants n=4 Participants
Region of Enrollment United Kingdom	102 Participants n=5 Participants	311 Participants n=7 Participants	315 Participants n=5 Participants	728 Participants n=4 Participants
Region of Enrollment Australia	56 Participants n=5 Participants	215 Participants n=7 Participants	218 Participants n=5 Participants	489 Participants n=4 Participants
Region of Enrollment Switzerland	3 Participants n=5 Participants	18 Participants n=7 Participants	18 Participants n=5 Participants	39 Participants n=4 Participants
Region of Enrollment Germany	2 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	21 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to the end of study (approximately up to 5 years)

Population: Full Analysis Set (FAS) included all participants who were randomized, received at least 1 dose of study drug, and at least 1 valid postbaseline value for assessment of primary efficacy. A participant who does not have an event of MCI due to AD was censored at the date of the last visit at which MCI due to AD could have been assessed.

Outcome measures

Outcome measures
Measure	Low Risk Placebo n=402 Participants Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to low risk group for developing MCI-AD for up to 5 years.	High Risk Placebo n=1406 Participants Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.
Time to Diagnosis of Mild Cognitive Impairment Due to Alzheimer's Disease (MCI-AD) for Placebo-treated, High-risk, Non-Hispanic/Latino Caucasian Participants Versus Placebo-treated, Low-risk, Non-Hispanic/Latino Caucasian Participants	905.44 days Interval 189.0 to 909.0	1238.67 days Interval 168.0 to 1268.0

PRIMARY outcome

Timeframe: Baseline to the end of study (approximately up to 5 years)

Population: FAS included all participants who were randomized, received at least 1 dose of study drug, and at least 1 valid postbaseline value for assessment of primary efficacy. A participant who does not have an event of MCI due to AD was censored at the date of the last visit at which MCI due to AD could have been assessed.

Outcome measures

Outcome measures
Measure	Low Risk Placebo n=1406 Participants Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to low risk group for developing MCI-AD for up to 5 years.	High Risk Placebo n=1430 Participants Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.
Time to Diagnosis of MCI Due to AD for Pioglitazone-treated, High-risk, Non-Hispanic/Latino Caucasian Participants Versus Placebo-treated, High-risk, Non-Hispanic/Latino, Caucasian Participants	1238.67 days Interval 168.0 to 1268.0	1261.24 days Interval 168.0 to 1285.0

SECONDARY outcome

Timeframe: Baseline and Month 48

Population: FAS included all participants who were randomized, received at least 1 dose of study drug, and at least 1 valid postbaseline value for assessment of primary efficacy. Number analyzed is the number of participants with evaluable data at the given time-point.

Composite scores derived from the test battery. Domains of Episodic Memory \[California Verbal Learning Test-2nd Edition (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R)\]; Executive Function \[Trail Making Test (TMT) (Part B), Wechsler Adult Intelligence Scale (WAIS)-III Digit Span Test-backwards span\]; Language \[Multilingual Naming Test (MiNT), Semantic Fluency (animals), Lexical/phonemic fluency (F, A, and S in English; D, S, and F in German)\]; and Attention \[WAIS-III Digit Span Test-forward span, TMT (Part A)\] used for composite score. 12 measures were derived from 8 neuropsychological tests. CVLT-II test involved 2 primary measures (short, long delay recall); BVMT-R had 2 measures (copy and recall); Digit Span and Trail both had 2 measures (forward and backward span and Parts A and B). There was 1 total score for each test: CDT, MINT, semantic and lexical fluency. Total score ranged from -1.222 to 1.707 at baseline, a higher composite score indicated better cognition.

Outcome measures

Outcome measures
Measure	Low Risk Placebo n=1406 Participants Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to low risk group for developing MCI-AD for up to 5 years.	High Risk Placebo n=1430 Participants Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.
Change From Baseline for Cognitive Decline on Composite Score on the Cognitive Test Battery for Pioglitazone-treated Participants Versus Placebo-treated Participants in the High-risk Stratum	0.1841 score on a scale Standard Deviation 0.27508	0.1687 score on a scale Standard Deviation 0.40621

SECONDARY outcome

Timeframe: Baseline and Month 48

Population: FAS included all participants who were randomized, received at least 1 dose of study drug, and at least 1 valid postbaseline value for assessment of primary efficacy. Number analyzed is the number of participants with evaluable data at the given time-point.

The ADCS ADL-PI is a functional measure that was specifically designed for standardized administration over long duration clinical studies to prevent AD. The ADCS ADL-PI is a 20-item instrument that included 15 ADL questions, which were scored as 1 (with a lot of difficulty), 2 (with some difficulty), or 3 (as well as usually, with no difficulty), plus 5 vision, hearing, and mobility questions, which were scored from 0 (no) to 1 (yes). ADL Total ranged from 0 to 45, and lower scores indicated greater disability.

Outcome measures

Outcome measures
Measure	Low Risk Placebo n=1406 Participants Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to low risk group for developing MCI-AD for up to 5 years.	High Risk Placebo n=1430 Participants Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.
Change From Baseline in Instrumental Activities of Daily Living (Alzheimer's Disease Cooperative Study Activities of Daily Living - Prevention Instrument [ADCS ADL-PI]) Between Pioglitazone-treated and Placebo-treated Groups of the High-risk Stratum	0.1 score on a scale Standard Deviation 4.93	0.3 score on a scale Standard Deviation 5.32

Adverse Events

Low Risk Placebo

Serious events: 81 serious events

Other events: 235 other events

Deaths: 2 deaths

High Risk Placebo

Serious events: 404 serious events

Other events: 828 other events

Deaths: 21 deaths

High Risk Pioglitazone

Serious events: 358 serious events

Other events: 822 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Low Risk Placebo n=427 participants at risk Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to low risk group for developing MCI-AD for up to 5 years.	High Risk Placebo n=1507 participants at risk Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.	High Risk Pioglitazone n=1531 participants at risk Pioglitazone 0.8 mg, sustained release (SR) tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.
Eye disorders Cataract	6.3% 27/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	7.9% 119/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	6.9% 106/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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	5.6% 24/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	4.6% 70/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	4.7% 72/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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	14.5% 62/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	12.6% 190/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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% 183/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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 Urinary tract infection	11.0% 47/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	11.8% 178/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	12.5% 191/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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	5.2% 22/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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% 72/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	5.9% 90/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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 Sinusitis	5.2% 22/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	4.4% 67/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	3.4% 52/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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 Fall	4.2% 18/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	9.5% 143/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	8.8% 135/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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 Arthralgia	10.5% 45/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	8.3% 125/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	8.2% 125/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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	7.3% 31/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	5.4% 82/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	6.6% 101/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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 Osteoarthritis	4.4% 19/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	5.4% 81/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	5.6% 86/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	5.4% 23/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	3.9% 59/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	4.6% 71/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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	4.7% 20/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	5.2% 79/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	5.0% 76/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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 Hypertension	6.1% 26/427 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	6.4% 97/1507 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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.	6.1% 93/1531 • Baseline up to 30 days after the last dose of study drug (up to 935 days) 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: [email protected]

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