Diabetes Mellitus and Gastroparesis, Idiopathic Gastroparesis
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to evaluate the safety, PK and PD of TAK-906 in participants with Gastroparesis (GP).
Detailed description
The drug being tested in this study is called TAK-906 maleate. TAK-906 maleate is being tested to treat people who have DG or IG. This study will assess the safety, tolerability, PK/PD and food effect of TAK-906 and will determine the effect of TAK-906 on gastric emptying (GE). The study enrolled a total of 51 participants. This study will be conducted in two parts: Part 1 and Part 2. Part 1 will consist of 48 participants enrolled in 3 active treatment groups and 1 placebo group. Participants in Part 1 will be randomly assigned (by chance, like flipping a coin) to one of the 3 active treatment groups or 1 placebo group-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): * TAK 906 maleate 5 mg * TAK 906 maleate 25 mg * TAK 906 maleate 100 mg * Placebo All participants who will complete Part 1 of the study will be eligible for enrollment in Part 2. Part 2 consisted of 21 participants who completed Part 1 and were assigned to the 2 open-label treatment groups as follow: * TAK-906 maleate 25 mg Fed + TAK-906 maleate 25 mg Fasted: crossover design, with a minimum 7-day washout in doses of each period. * Metoclopramide 10 mg This multi-center trial will be conducted the United States. The overall time to participate in this study is approximately 8 weeks. Participants will make a final visit to the clinic 10-14 days after receiving their last dose of study drug for a follow-up assessment.
Interventions
DRUGTAK-906 Maleate
TAK-906 Maleate Capsules
DRUGMetaclopramide
Metaclopramide Tablets
DRUGTAK-906 Maleate Placebo
TAK-906 placebo-matching Capsules
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The study has two parts: Part 1 (double-blind) and Part 2 (open-label).
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
In order to be eligible for participation in this trial, the participant must: 1. Has a documented diagnosis of diabetes mellitus gastroparesis (DG) or idiopathic gastroparesis (IG). 2. Has a body mass index (BMI) greater than or equal to (\>=) 18 and less than or equal to (\<=) 40 kilogram per square meter (kg/m\^2) at the Screening Visit. 3. Be a non-smoker who has not used tobacco or nicotine-containing products (example, nicotine patch) for at least 6 months prior to trial drug administration of the initial dose of trial drug/invasive procedure. 4. Has symptoms for gastroparesis (GP) (that is, chronic postprandial fullness, abdominal pain, postprandial nausea, vomiting, loss of appetite and/or early satiety) the past 3 months. 5. Has documented slow gastric emptying (GE), with delayed GE by 13C-Spirulina gastric emptying breath test (GEBT) at Screening defined as \>=80th percentile. Note: If a participant has had a documented scintigraphy or GEBT within the last 12 months that confirms the diagnosis of delayed GE, a screening GEBT would not be required. 6. Has nausea subscale (of American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary \[ANMS-GCSI-DD\]) symptom score \>=2 at least 3 of 7 days during Screening. 7. Has haemoglobin A1c (HBA1c) less than (\<) 10 percent (%) (for diabetes mellitus only).
Exclusion criteria
The participant must be excluded from participating in the trial if the participant: 1. Has acute severe gastroenteritis and pronounced dehydration in the past 48 hours prior to Screening, gastric pacemaker, chronic parenteral feeding or persistent severe vomiting. 2. Has a known disturbance of small intestinal absorption, exocrine pancreatic function, liver metabolism, and pulmonary function. 3. Has a history of anorexia nervosa or bulimia. 4. Previous history of bezoars (the presence of retained liquid, bile, or small amounts of poorly organized food residue is permitted). 5. Difficulty swallowing solid food or pills. 6. Prior surgery involving the luminal gastrointestinal (GI) tract (cholecystectomy, appendectomy, and hysterectomy are permitted if performed greater than (\>) 3 months prior to SmartPill test). 7. Any abdominal or pelvic surgery within the past 3 months. 8. Known or history of inflammatory bowel disease. 9. Has active diverticulitis, diverticular stricture, and other intestinal strictures. 10. Had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter \[mL\]) within 4 weeks prior to the pretrial (screening) visit milligram per deciliter (mg/dL) (14.99 millimole per liter \[mmol/L\]) during any visit up to and including the randomization visit (Period 1 Day 1 predose). Note: If the participant meets this exclusion criterion and the investigator believes that the value is not consistent with the participant's current self-monitoring blood glucose values, the participant should not be excluded at this time. The visit can be repeated within 5 to 7 days. 11. Has had diabetic ketoacidosis (within the prior 4 weeks).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A SAE is an AE resulting in any of the following outcomes or deemed significant for any following reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. |
| Number of Participants With Markedly Abnormal Laboratory Parameters Values | From Baseline to 14 days after the last dose of study drug in Part 1 (Up to approximately 23 days) | Clinical Laboratory parameters included tests for chemistry, hematology and urinalysis. Markedly abnormal values during treatment period were categorized as:alanine aminotransferase (ALT)\>3.0 U/L\*upper limit of normal(ULN),albumin\<25 g/L\*lower limit of normal(LLN),alkaline phosphatase \>3.0 U/L\*ULN,aspartate aminotransferase \>3.0 U/L\*ULN,bilirubin \>2 umol/L\*ULN,blood urea nitrogen(BUN) \>10.7 mmol/L,calcium \<1.75 mmol/L, \>2.88 mmol/L,chloride \<75 mmol/L, \>126 mmol/L,creatinine \>177umol/L,gamma glutamyl transferase (GGT) \>3 U/L\*ULN,glucose \<2.8 mmol/L, \>19.4 mmol/L,phosphate \<0.52 mmol/L, \>2.10 mmol/L,potassium\<3 mmol/L, \>6 mmol/L,sodium \<130 mmol/L, \>150 mmol/L,hematocrit (%) \<0.8\*LLN, \>1.2\*ULN,hemoglobin \<0.8 g/L\*LLN, \>1.2 g/L\*ULN,leukocytes \<0.5 (10\^9/L)\*LLN, \>1.5 (10\^9/L)\*ULN,erythrocytes\<0.8 (10\^12/L)\*LLN, \>1.2(10\^12/L)\*ULN,platelets \<75(10\^9/L), \>600(10\^9/L). Participants with at least 1 markedly abnormal laboratory parameter value is reported. |
| Number of Participants With Markedly Abnormal Vital Signs | From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days) | Vital signs included body temperature, diastolic and systolic blood pressure (mmHg), and heart rate (beats per minute \[bpm\]). Heart rate\<50 bpm and systolic blood pressure \<85 mmHg were considered markedly abnormal. |
| Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days) | The 12-lead electrocardiogram (ECG) values outside the range Heart Rate \<50 (beats/min), PR Interval ≤120 (msec), PR Interval ≥200 (msec), QRS Duration ≥120 (msec), QT Interval ≥460 (msec) were considered markedly abnormal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUCτ: Area Under the Plasma Concentration-time Curve From 0 to Time (T) Over the Dosing Interval for TAK-906 in Part 1 | Part 1: Day 1 predose and at multiple timepoints, (Up to 8 hours) postdose and Day 7 predose and at multiple timepoints (Up to 48 hours) postdose | — |
| Cmax: Maximum Observed Plasma Concentration for TAK 906 in Part 1 | Part 1: Day 1 predose and at multiple timepoints, (Up to 8 hours) postdose and Day 7 predose and at multiple timepoints (Up to 48 hours) postdose | — |
| Change From Baseline in Serum Prolactin Concentration on Day 1 at Tmax, Time of First Occurrence of Maximum Serum Concentration (Cmax) for TAK-906 Maleate for Part 1 | Day 1 predose (Baseline), 1 hour and at multiple timepoints (Up to 8 hours) postdose | Change in serum prolactin on Day 1 at the Tmax, time of first occurrence of maximum serum concentration (Cmax) relative to Baseline was calculated as a ratio of maximum serum prolactin concentration on Day 1 to serum prolactin concentration at Baseline. |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 in Part 1 | Part 1: Day 1 predose and at multiple timepoints, (Up to 8 hours) postdose and Day 7 predose and at multiple timepoints (Up to 48 hours) postdose | — |
| Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Part 1: Predose on Days 2, 3, 4, 5, 6, 7, 8 and 9 | — |
| Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time as Measured by the 13C Spirulina GEBT Following Multiple Dose Administration of TAK-906 Maleate on Day 7 for Part 1 | Baseline and Day 7 | The GEBT is a nonradioactive, noninvasive, orally administered test for measuring the rate of solid phase gastric emptying (GE) in adults. The GEBT measures how fast solid food moves from the stomach to the small intestine during the digestive process and aids in the diagnosis of delayed stomach emptying (GP). GE half-emptying time is the time in minutes (min) for half of the ingested solids to leave the stomach. This value was measured by the 13C spirulina GEBT. |
| Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time Following Single Dose Administration of TAK-906 Maleate as Measured by the 13C Spirulina GEBT on Day 1 | Baseline and Day 1 of Part 1 | The GEBT is a nonradioactive, noninvasive, orally administered test for measuring the rate of solid phase gastric emptying (GE) in adults. The GEBT measures how fast solid food moves from the stomach to the small intestine during the digestive process and aids in the diagnosis of delayed stomach emptying (GP). GE half-emptying time is the time in minutes (min) for half of the ingested solids to leave the stomach. This value was measured by the 13C spirulina GEBT. |
| Percent Change From Baseline in Gastric Emptying (GE) Time as Measured by the SmartPill on Day 7 for Part 1 | Baseline and Day 7 | SmartPill is an ingestible capsule that measures pressure, potential of hydrogen (pH) and temperature as it travels through the gastrointestinal (GI) tract to assess GE and GI motility. SmartPill eliminates radiation exposure and is the only motility test that provides a complete transit profile of the GI tract. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 7 investigative sites in the United States from 26 September 2017 to 09 March 2018.
Pre-assignment details
Participants with a diagnosis of diabetes mellitus and gastroparesis (GP) or with idiopathic gastroparesis (IG) were enrolled. 51 participants were randomized in Part 1, out of which 48 completed the Part 1, 21 of 48 participants entered the Part 2.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Placebo TAK-906 placebo-matching (4x0 mg), capsule, orally, twice daily (BID) on Days 1-8 and once on Day 9 under fasted conditions. | 12 |
| Part 1: TAK 906 Maleate 5 mg TAK-906 maleate 1x5 mg, capsule, orally, BID and TAK-906 maleate placebo-matching (3x0 mg), capsules, orally, BID on Days 1-8, followed by TAK-906 maleate 1x5 mg, capsule, orally once on Day 9 under fasted conditions. | 14 |
| Part 1: TAK 906 Maleate 25 mg TAK-906 maleate 1x25 mg, capsule, orally, BID and TAK-906 maleate placebo-matching (3x0 mg), capsules, orally, BID on Days 1-8 followed by TAK-906 maleate 1x25 mg, capsule, orally, once on Day 9 under fasted conditions. | 12 |
| Part 1: TAK 906 Maleate 100 mg TAK-906 maleate 100 mg (4x25 mg), capsules, orally, BID on Days 1-8 and once a day on Day 9 under fasted conditions. | 13 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Part 1 (Days 1 to 9) | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part 1 (Days 1 to 9) | Protocol Deviation | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1 (Days 1 to 9) | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part 2: Days 17 to 25 | Reason not specified | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part 2: Days 17 to 25 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: Placebo | Part 1: TAK 906 Maleate 5 mg | Part 1: TAK 906 Maleate 25 mg | Part 1: TAK 906 Maleate 100 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 49.9 years STANDARD_DEVIATION 13.84 | 54.7 years STANDARD_DEVIATION 11.75 | 52.7 years STANDARD_DEVIATION 17.13 | 55.9 years STANDARD_DEVIATION 10.19 | 53.4 years STANDARD_DEVIATION 13.14 |
| Body Mass Index (BMI) | 27.282 kg/m^2 STANDARD_DEVIATION 4.2276 | 29.679 kg/m^2 STANDARD_DEVIATION 4.5043 | 29.832 kg/m^2 STANDARD_DEVIATION 4.5461 | 32.565 kg/m^2 STANDARD_DEVIATION 4.4001 | 29.887 kg/m^2 STANDARD_DEVIATION 4.6805 |
| Height | 164.62 cm STANDARD_DEVIATION 9.79 | 163.95 cm STANDARD_DEVIATION 6.751 | 164.56 cm STANDARD_DEVIATION 7.204 | 164.93 cm STANDARD_DEVIATION 9.778 | 164.50 cm STANDARD_DEVIATION 8.212 |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 4 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 9 Participants | 5 Participants | 3 Participants | 7 Participants | 24 Participants |
| Race/Ethnicity, Customized Multiracial | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Non-Hispanic and Latino | 3 Participants | 9 Participants | 9 Participants | 6 Participants | 27 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 13 Participants | 7 Participants | 11 Participants | 42 Participants |
| Region of Enrollment United States | 12 Participants | 14 Participants | 12 Participants | 13 Participants | 51 Participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 10 Participants | 10 Participants | 40 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 11 Participants |
| Underlying Disease Diabetic Gastroparesis (DG) | 8 Participants | 10 Participants | 8 Participants | 8 Participants | 34 Participants |
| Underlying Disease Idiopathic Gastroparesis (IG) | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 17 Participants |
| Weight | 74.70 kg STANDARD_DEVIATION 17.231 | 79.86 kg STANDARD_DEVIATION 13.47 | 80.55 kg STANDARD_DEVIATION 11.346 | 88.24 kg STANDARD_DEVIATION 11.803 | 80.95 kg STANDARD_DEVIATION 14.064 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 14 | 0 / 12 | 0 / 13 | 0 / 6 | 0 / 6 | 0 / 13 |
| other Total, other adverse events | 3 / 12 | 4 / 14 | 3 / 12 | 4 / 13 | 1 / 6 | 0 / 6 | 1 / 13 |
| serious Total, serious adverse events | 1 / 12 | 0 / 14 | 0 / 12 | 1 / 13 | 0 / 6 | 0 / 6 | 0 / 13 |
Outcome results
Primary
Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A SAE is an AE resulting in any of the following outcomes or deemed significant for any following reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.
Time frame: From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days)
Population: SAS included all participants who were randomized (Part 1) or enrolled (Part 2) and received at least 1 dose of study drug in the respective part.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Placebo | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 4 Participants |
| Part 1: Placebo | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 4 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 3 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 4 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Part 2: TAK-906 Maleate 25 mg Fed Condition | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 1 Participants |
| Part 2: TAK-906 Maleate 25 mg Fed Condition | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fasted Condition | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fasted Condition | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Part 2: Metoclopramide 10 mg | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 1 Participants |
| Part 2: Metoclopramide 10 mg | Number of Participants Who Experienced At Least One or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Primary
Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values
The 12-lead electrocardiogram (ECG) values outside the range Heart Rate \<50 (beats/min), PR Interval ≤120 (msec), PR Interval ≥200 (msec), QRS Duration ≥120 (msec), QT Interval ≥460 (msec) were considered markedly abnormal.
Time frame: From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days)
Population: SAS included all participants who were randomized (Part 1) or enrolled (Part 2) and received at least 1 dose of study drug in the respective part.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Placebo | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≥200 | 1 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | Heart Rate (bpm) <50 | 1 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QT Interval (msec) ≥460 | 0 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≤120 | 0 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QRS Duration (msec) ≥120 | 0 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≥200 | 2 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≤120 | 1 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QRS Duration (msec) ≥120 | 0 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | Heart Rate (bpm) <50 | 1 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QT Interval (msec) ≥460 | 1 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QT Interval (msec) ≥460 | 0 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≤120 | 1 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | Heart Rate (bpm) <50 | 0 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≥200 | 1 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QRS Duration (msec) ≥120 | 2 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≥200 | 4 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | Heart Rate (bpm) <50 | 0 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≤120 | 1 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QRS Duration (msec) ≥120 | 0 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QT Interval (msec) ≥460 | 1 Participants |
| Part 2: TAK-906 Maleate 25 mg Fed Condition | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | Heart Rate (bpm) <50 | 1 Participants |
| Part 2: TAK-906 Maleate 25 mg Fed Condition | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QT Interval (msec) ≥460 | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fed Condition | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≥200 | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fed Condition | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QRS Duration (msec) ≥120 | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fed Condition | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≤120 | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fasted Condition | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | Heart Rate (bpm) <50 | 1 Participants |
| Part 2: TAK-906 Maleate 25 mg Fasted Condition | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QT Interval (msec) ≥460 | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fasted Condition | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QRS Duration (msec) ≥120 | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fasted Condition | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≤120 | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fasted Condition | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≥200 | 0 Participants |
| Part 2: Metoclopramide 10 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QRS Duration (msec) ≥120 | 0 Participants |
| Part 2: Metoclopramide 10 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≤120 | 1 Participants |
| Part 2: Metoclopramide 10 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | PR Interval (msec) ≥200 | 4 Participants |
| Part 2: Metoclopramide 10 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | Heart Rate (bpm) <50 | 0 Participants |
| Part 2: Metoclopramide 10 mg | Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values | QT Interval (msec) ≥460 | 0 Participants |
Primary
Number of Participants With Markedly Abnormal Laboratory Parameters Values
Clinical Laboratory parameters included tests for chemistry, hematology and urinalysis. Markedly abnormal values during treatment period were categorized as:alanine aminotransferase (ALT)\>3.0 U/L\*upper limit of normal(ULN),albumin\<25 g/L\*lower limit of normal(LLN),alkaline phosphatase \>3.0 U/L\*ULN,aspartate aminotransferase \>3.0 U/L\*ULN,bilirubin \>2 umol/L\*ULN,blood urea nitrogen(BUN) \>10.7 mmol/L,calcium \<1.75 mmol/L, \>2.88 mmol/L,chloride \<75 mmol/L, \>126 mmol/L,creatinine \>177umol/L,gamma glutamyl transferase (GGT) \>3 U/L\*ULN,glucose \<2.8 mmol/L, \>19.4 mmol/L,phosphate \<0.52 mmol/L, \>2.10 mmol/L,potassium\<3 mmol/L, \>6 mmol/L,sodium \<130 mmol/L, \>150 mmol/L,hematocrit (%) \<0.8\*LLN, \>1.2\*ULN,hemoglobin \<0.8 g/L\*LLN, \>1.2 g/L\*ULN,leukocytes \<0.5 (10\^9/L)\*LLN, \>1.5 (10\^9/L)\*ULN,erythrocytes\<0.8 (10\^12/L)\*LLN, \>1.2(10\^12/L)\*ULN,platelets \<75(10\^9/L), \>600(10\^9/L). Participants with at least 1 markedly abnormal laboratory parameter value is reported.
Time frame: From Baseline to 14 days after the last dose of study drug in Part 1 (Up to approximately 23 days)
Population: SAS included all participants who were randomized and received at least 1 dose of study drug in the Part 1. Laboratory assessment were performed only in Part 1 of the study. Number analyzed are participants with data available for the particular parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Placebo | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Hematocrit (%)<0.8 x LLN | 0 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Hemoglobin (g/L) <0.8 x LLN | 1 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Laboratory Parameters Values | ALT >3.0 U/Lx ULN | 0 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Laboratory Parameters Values | AST >3.0 U/L x ULN | 0 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Laboratory Parameters Values | BUN >10.7 mmol/L | 1 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Calcium >2.88 mmol/L | 0 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Laboratory Parameters Values | GGT >3 x ULN | 0 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Sodium (mmol/L) <130 mmol/L | 1 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Calcium >2.88 mmol/L | 0 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | BUN >10.7 mmol/L | 0 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Hemoglobin (g/L) <0.8 x LLN | 0 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Sodium (mmol/L) <130 mmol/L | 0 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | GGT >3 x ULN | 0 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | AST >3.0 U/L x ULN | 0 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | ALT >3.0 U/Lx ULN | 0 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Hematocrit (%)<0.8 x LLN | 1 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | GGT >3 x ULN | 0 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | ALT >3.0 U/Lx ULN | 1 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | AST >3.0 U/L x ULN | 1 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | BUN >10.7 mmol/L | 0 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Calcium >2.88 mmol/L | 0 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Sodium (mmol/L) <130 mmol/L | 0 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Hematocrit (%)<0.8 x LLN | 0 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Hemoglobin (g/L) <0.8 x LLN | 0 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | ALT >3.0 U/Lx ULN | 0 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | AST >3.0 U/L x ULN | 0 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Hemoglobin (g/L) <0.8 x LLN | 0 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Hematocrit (%)<0.8 x LLN | 0 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | BUN >10.7 mmol/L | 1 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Sodium (mmol/L) <130 mmol/L | 0 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | GGT >3 x ULN | 1 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Laboratory Parameters Values | Calcium >2.88 mmol/L | 1 Participants |
Primary
Number of Participants With Markedly Abnormal Vital Signs
Vital signs included body temperature, diastolic and systolic blood pressure (mmHg), and heart rate (beats per minute \[bpm\]). Heart rate\<50 bpm and systolic blood pressure \<85 mmHg were considered markedly abnormal.
Time frame: From Baseline to 14 days after the last dose of study drug (Up to approximately 39 days)
Population: SAS included all participants who were randomized (Part 1) or enrolled (Part 2) and received at least 1 dose of study drug in the respective part.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Placebo | Number of Participants With Markedly Abnormal Vital Signs | Systolic Blood Pressure (mmHg) <85 | 1 Participants |
| Part 1: Placebo | Number of Participants With Markedly Abnormal Vital Signs | Heart Rate (bpm) <50 | 0 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Vital Signs | Heart Rate (bpm) <50 | 1 Participants |
| Part 1: TAK 906 Maleate 5 mg | Number of Participants With Markedly Abnormal Vital Signs | Systolic Blood Pressure (mmHg) <85 | 0 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Vital Signs | Heart Rate (bpm) <50 | 0 Participants |
| Part 1: TAK 906 Maleate 25 mg | Number of Participants With Markedly Abnormal Vital Signs | Systolic Blood Pressure (mmHg) <85 | 0 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Vital Signs | Systolic Blood Pressure (mmHg) <85 | 0 Participants |
| Part 1: TAK 906 Maleate 100 mg | Number of Participants With Markedly Abnormal Vital Signs | Heart Rate (bpm) <50 | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fed Condition | Number of Participants With Markedly Abnormal Vital Signs | Heart Rate (bpm) <50 | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fed Condition | Number of Participants With Markedly Abnormal Vital Signs | Systolic Blood Pressure (mmHg) <85 | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fasted Condition | Number of Participants With Markedly Abnormal Vital Signs | Heart Rate (bpm) <50 | 0 Participants |
| Part 2: TAK-906 Maleate 25 mg Fasted Condition | Number of Participants With Markedly Abnormal Vital Signs | Systolic Blood Pressure (mmHg) <85 | 0 Participants |
| Part 2: Metoclopramide 10 mg | Number of Participants With Markedly Abnormal Vital Signs | Systolic Blood Pressure (mmHg) <85 | 0 Participants |
| Part 2: Metoclopramide 10 mg | Number of Participants With Markedly Abnormal Vital Signs | Heart Rate (bpm) <50 | 0 Participants |
Secondary
AUCτ: Area Under the Plasma Concentration-time Curve From 0 to Time (T) Over the Dosing Interval for TAK-906 in Part 1
Time frame: Part 1: Day 1 predose and at multiple timepoints, (Up to 8 hours) postdose and Day 7 predose and at multiple timepoints (Up to 48 hours) postdose
Population: Pharmacokinetic (PK) set included participants who were randomized and received at least 1 dose of study drug and had at least 1 measurable plasma TAK-906 concentration. Overall number of participants analyzed are participants with data available for analysis of AUCt. Number analyzed are participants with evaluable data at given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | AUCτ: Area Under the Plasma Concentration-time Curve From 0 to Time (T) Over the Dosing Interval for TAK-906 in Part 1 | Day 1 | 4.67 h*ng/mL | Standard Deviation 1.69 |
| Part 1: Placebo | AUCτ: Area Under the Plasma Concentration-time Curve From 0 to Time (T) Over the Dosing Interval for TAK-906 in Part 1 | Day 7 | 5.46 h*ng/mL | Standard Deviation 2.07 |
| Part 1: TAK 906 Maleate 5 mg | AUCτ: Area Under the Plasma Concentration-time Curve From 0 to Time (T) Over the Dosing Interval for TAK-906 in Part 1 | Day 1 | 23.0 h*ng/mL | Standard Deviation 7.76 |
| Part 1: TAK 906 Maleate 5 mg | AUCτ: Area Under the Plasma Concentration-time Curve From 0 to Time (T) Over the Dosing Interval for TAK-906 in Part 1 | Day 7 | 26.3 h*ng/mL | Standard Deviation 11.3 |
| Part 1: TAK 906 Maleate 25 mg | AUCτ: Area Under the Plasma Concentration-time Curve From 0 to Time (T) Over the Dosing Interval for TAK-906 in Part 1 | Day 1 | 131 h*ng/mL | Standard Deviation 44.8 |
| Part 1: TAK 906 Maleate 25 mg | AUCτ: Area Under the Plasma Concentration-time Curve From 0 to Time (T) Over the Dosing Interval for TAK-906 in Part 1 | Day 7 | 166 h*ng/mL | Standard Deviation 93 |
Secondary
Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time as Measured by the 13C Spirulina GEBT Following Multiple Dose Administration of TAK-906 Maleate on Day 7 for Part 1
The GEBT is a nonradioactive, noninvasive, orally administered test for measuring the rate of solid phase gastric emptying (GE) in adults. The GEBT measures how fast solid food moves from the stomach to the small intestine during the digestive process and aids in the diagnosis of delayed stomach emptying (GP). GE half-emptying time is the time in minutes (min) for half of the ingested solids to leave the stomach. This value was measured by the 13C spirulina GEBT.
Time frame: Baseline and Day 7
Population: FAS included all participants who were randomized (Part 1), received at least 1 dose of study drug, had a baseline value, and had at least 1 valid postbaseline value for assessment of at least one of the PD measurement. Overall number of participants analyzed are the participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time as Measured by the 13C Spirulina GEBT Following Multiple Dose Administration of TAK-906 Maleate on Day 7 for Part 1 | Baseline | 118.74 min | Standard Deviation 43.106 |
| Part 1: Placebo | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time as Measured by the 13C Spirulina GEBT Following Multiple Dose Administration of TAK-906 Maleate on Day 7 for Part 1 | Change from Baseline at Day 7 | 4.55 min | Standard Deviation 16.332 |
| Part 1: TAK 906 Maleate 5 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time as Measured by the 13C Spirulina GEBT Following Multiple Dose Administration of TAK-906 Maleate on Day 7 for Part 1 | Change from Baseline at Day 7 | 6.21 min | Standard Deviation 36.986 |
| Part 1: TAK 906 Maleate 5 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time as Measured by the 13C Spirulina GEBT Following Multiple Dose Administration of TAK-906 Maleate on Day 7 for Part 1 | Baseline | 130.18 min | Standard Deviation 35.316 |
| Part 1: TAK 906 Maleate 25 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time as Measured by the 13C Spirulina GEBT Following Multiple Dose Administration of TAK-906 Maleate on Day 7 for Part 1 | Baseline | 121.26 min | Standard Deviation 33.606 |
| Part 1: TAK 906 Maleate 25 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time as Measured by the 13C Spirulina GEBT Following Multiple Dose Administration of TAK-906 Maleate on Day 7 for Part 1 | Change from Baseline at Day 7 | 7.80 min | Standard Deviation 52.946 |
| Part 1: TAK 906 Maleate 100 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time as Measured by the 13C Spirulina GEBT Following Multiple Dose Administration of TAK-906 Maleate on Day 7 for Part 1 | Baseline | 122.50 min | Standard Deviation 31.803 |
| Part 1: TAK 906 Maleate 100 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time as Measured by the 13C Spirulina GEBT Following Multiple Dose Administration of TAK-906 Maleate on Day 7 for Part 1 | Change from Baseline at Day 7 | 7.72 min | Standard Deviation 24.609 |
Comparison: Change from Baseline in GEBT gastric half-emptying time on Day 7 in Part 1.p-value: 0.59995% CI: [-21.89, 37.41]ANCOVA
Comparison: Change from Baseline in GEBT gastric half-emptying time on Day 7 in Part 1.p-value: 0.68795% CI: [-25.04, 37.59]ANCOVA
Comparison: Change from Baseline in GEBT gastric half-emptying time on Day 7 in Part 1.p-value: 0.60595% CI: [-23.22, 39.33]ANCOVA
Secondary
Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time Following Single Dose Administration of TAK-906 Maleate as Measured by the 13C Spirulina GEBT on Day 1
The GEBT is a nonradioactive, noninvasive, orally administered test for measuring the rate of solid phase gastric emptying (GE) in adults. The GEBT measures how fast solid food moves from the stomach to the small intestine during the digestive process and aids in the diagnosis of delayed stomach emptying (GP). GE half-emptying time is the time in minutes (min) for half of the ingested solids to leave the stomach. This value was measured by the 13C spirulina GEBT.
Time frame: Baseline and Day 1 of Part 1
Population: FAS included all participants who were randomized (Part 1), received at least 1 dose of study drug, had a baseline at least 1 valid postbaseline value for assessment of at least one PD measurement. Overall number of participants analyzed are participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time Following Single Dose Administration of TAK-906 Maleate as Measured by the 13C Spirulina GEBT on Day 1 | Baseline | 118.74 minute (min) | Standard Deviation 43.106 |
| Part 1: Placebo | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time Following Single Dose Administration of TAK-906 Maleate as Measured by the 13C Spirulina GEBT on Day 1 | Change from Baseline at Day 1 | -5.71 minute (min) | Standard Deviation 21.687 |
| Part 1: TAK 906 Maleate 5 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time Following Single Dose Administration of TAK-906 Maleate as Measured by the 13C Spirulina GEBT on Day 1 | Change from Baseline at Day 1 | 0.12 minute (min) | Standard Deviation 21.736 |
| Part 1: TAK 906 Maleate 5 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time Following Single Dose Administration of TAK-906 Maleate as Measured by the 13C Spirulina GEBT on Day 1 | Baseline | 130.18 minute (min) | Standard Deviation 35.316 |
| Part 1: TAK 906 Maleate 25 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time Following Single Dose Administration of TAK-906 Maleate as Measured by the 13C Spirulina GEBT on Day 1 | Baseline | 121.26 minute (min) | Standard Deviation 33.606 |
| Part 1: TAK 906 Maleate 25 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time Following Single Dose Administration of TAK-906 Maleate as Measured by the 13C Spirulina GEBT on Day 1 | Change from Baseline at Day 1 | 6.74 minute (min) | Standard Deviation 44.39 |
| Part 1: TAK 906 Maleate 100 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time Following Single Dose Administration of TAK-906 Maleate as Measured by the 13C Spirulina GEBT on Day 1 | Baseline | 122.50 minute (min) | Standard Deviation 31.803 |
| Part 1: TAK 906 Maleate 100 mg | Change From Baseline in Gastric Emptying Breath Test (GEBT) Gastric Half-emptying Time Following Single Dose Administration of TAK-906 Maleate as Measured by the 13C Spirulina GEBT on Day 1 | Change from Baseline at Day 1 | 0.71 minute (min) | Standard Deviation 21.192 |
Comparison: Change from Baseline in GEBT gastric half-emptying time on Day 1 in Part 1.p-value: 0.52295% CI: [-16.06, 31.19]ANCOVA
Comparison: Change from Baseline in GEBT gastric half-emptying time on Day 1 in Part 1.p-value: 0.29395% CI: [-11.58, 37.43]ANCOVA
Comparison: Change from Baseline in GEBT gastric half-emptying time on Day 1 in Part 1.p-value: 0.55195% CI: [-16.52, 30.52]ANCOVA
Secondary
Change From Baseline in Serum Prolactin Concentration on Day 1 at Tmax, Time of First Occurrence of Maximum Serum Concentration (Cmax) for TAK-906 Maleate for Part 1
Change in serum prolactin on Day 1 at the Tmax, time of first occurrence of maximum serum concentration (Cmax) relative to Baseline was calculated as a ratio of maximum serum prolactin concentration on Day 1 to serum prolactin concentration at Baseline.
Time frame: Day 1 predose (Baseline), 1 hour and at multiple timepoints (Up to 8 hours) postdose
Population: Full analysis set (FAS) included all participants who were randomized (Part 1), received at least 1 dose of study drug, had a baseline value, and had at least 1 valid postbaseline value for at least one of pharmacodynamic (PD) measurement. Overall number of participants analyzed are participants with evaluable data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo | Change From Baseline in Serum Prolactin Concentration on Day 1 at Tmax, Time of First Occurrence of Maximum Serum Concentration (Cmax) for TAK-906 Maleate for Part 1 | 1.54 ratio | Standard Deviation 0.704 |
| Part 1: TAK 906 Maleate 5 mg | Change From Baseline in Serum Prolactin Concentration on Day 1 at Tmax, Time of First Occurrence of Maximum Serum Concentration (Cmax) for TAK-906 Maleate for Part 1 | 12.77 ratio | Standard Deviation 9.102 |
| Part 1: TAK 906 Maleate 25 mg | Change From Baseline in Serum Prolactin Concentration on Day 1 at Tmax, Time of First Occurrence of Maximum Serum Concentration (Cmax) for TAK-906 Maleate for Part 1 | 19.92 ratio | Standard Deviation 13.604 |
| Part 1: TAK 906 Maleate 100 mg | Change From Baseline in Serum Prolactin Concentration on Day 1 at Tmax, Time of First Occurrence of Maximum Serum Concentration (Cmax) for TAK-906 Maleate for Part 1 | 20.07 ratio | Standard Deviation 9.17 |
Comparison: Change in serum prolactin on Day 1 at the Tmax as a ratio of Cmax to serum prolactin concentration at Baseline.p-value: <0.00195% CI: [4.03, 13.52]ANCOVA
Comparison: Change in serum prolactin on Day 1 at the Tmax as a ratio of Cmax to serum prolactin concentration at Baseline.p-value: <0.00195% CI: [5.91, 21.41]ANCOVA
Comparison: Change in serum prolactin on Day 1 at the Tmax as a ratio of Cmax to serum prolactin concentration at Baseline.p-value: <0.00195% CI: [6.94, 23.59]ANCOVA
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK 906 in Part 1
Time frame: Part 1: Day 1 predose and at multiple timepoints, (Up to 8 hours) postdose and Day 7 predose and at multiple timepoints (Up to 48 hours) postdose
Population: PK set included participants who were randomized and received at least 1 dose of study drug and had at least 1 measurable plasma TAK-906 concentration. Overall number of participants analyzed are participants with data available for analysis of Cmax. Number analyzed are participants with evaluable data at given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Cmax: Maximum Observed Plasma Concentration for TAK 906 in Part 1 | Day 1 | 2.27 ng/mL | Standard Deviation 0.819 |
| Part 1: Placebo | Cmax: Maximum Observed Plasma Concentration for TAK 906 in Part 1 | Day 7 | 2.87 ng/mL | Standard Deviation 1.78 |
| Part 1: TAK 906 Maleate 5 mg | Cmax: Maximum Observed Plasma Concentration for TAK 906 in Part 1 | Day 1 | 12.0 ng/mL | Standard Deviation 5.36 |
| Part 1: TAK 906 Maleate 5 mg | Cmax: Maximum Observed Plasma Concentration for TAK 906 in Part 1 | Day 7 | 15.5 ng/mL | Standard Deviation 5.58 |
| Part 1: TAK 906 Maleate 25 mg | Cmax: Maximum Observed Plasma Concentration for TAK 906 in Part 1 | Day 1 | 75.7 ng/mL | Standard Deviation 39.9 |
| Part 1: TAK 906 Maleate 25 mg | Cmax: Maximum Observed Plasma Concentration for TAK 906 in Part 1 | Day 7 | 99.6 ng/mL | Standard Deviation 69.4 |
Secondary
Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1
Time frame: Part 1: Predose on Days 2, 3, 4, 5, 6, 7, 8 and 9
Population: PK set included participants who were randomized and received at least 1 dose of study drug and had at least 1 measurable plasma TAK-906 concentration. Overall number of participants analyzed are participants with data available for analysis of Ctrough. Number analyzed are participants with evaluable data at given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Placebo | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 9 | 0.0700 ng/mL | Standard Deviation 0.12 |
| Part 1: Placebo | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 4 | 0.0178 ng/mL | Standard Deviation 0.0503 |
| Part 1: Placebo | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 8 | 0.0763 ng/mL | Standard Deviation 0.1 |
| Part 1: Placebo | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 2 | 0.0121 ng/mL | Standard Deviation 0.0315 |
| Part 1: Placebo | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 5 | 0.0457 ng/mL | Standard Deviation 0.0962 |
| Part 1: Placebo | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 6 | 0.0423 ng/mL | Standard Deviation 0.0502 |
| Part 1: Placebo | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 3 | 0.0423 ng/mL | Standard Deviation 0.0527 |
| Part 1: Placebo | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 7 | 0.0596 ng/mL | Standard Deviation 0.0905 |
| Part 1: TAK 906 Maleate 5 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 6 | 0.412 ng/mL | Standard Deviation 0.415 |
| Part 1: TAK 906 Maleate 5 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 3 | 0.503 ng/mL | Standard Deviation 0.64 |
| Part 1: TAK 906 Maleate 5 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 8 | 0.522 ng/mL | Standard Deviation 0.648 |
| Part 1: TAK 906 Maleate 5 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 2 | 0.262 ng/mL | Standard Deviation 0.349 |
| Part 1: TAK 906 Maleate 5 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 9 | 0.280 ng/mL | Standard Deviation 0.243 |
| Part 1: TAK 906 Maleate 5 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 7 | 0.336 ng/mL | Standard Deviation 0.383 |
| Part 1: TAK 906 Maleate 5 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 4 | 0.302 ng/mL | Standard Deviation 0.214 |
| Part 1: TAK 906 Maleate 5 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 5 | 1.09 ng/mL | Standard Deviation 1.97 |
| Part 1: TAK 906 Maleate 25 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 9 | 1.40 ng/mL | Standard Deviation 1.08 |
| Part 1: TAK 906 Maleate 25 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 2 | 0.770 ng/mL | Standard Deviation 0.513 |
| Part 1: TAK 906 Maleate 25 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 3 | 0.958 ng/mL | Standard Deviation 0.75 |
| Part 1: TAK 906 Maleate 25 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 4 | 1.17 ng/mL | Standard Deviation 0.799 |
| Part 1: TAK 906 Maleate 25 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 6 | 1.01 ng/mL | Standard Deviation 0.469 |
| Part 1: TAK 906 Maleate 25 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 7 | 1.48 ng/mL | Standard Deviation 0.936 |
| Part 1: TAK 906 Maleate 25 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 8 | 1.16 ng/mL | Standard Deviation 0.878 |
| Part 1: TAK 906 Maleate 25 mg | Ctrough: Observed Concentration at the End of a Dosing Interval for TAK-906 in Part 1 | Predose on Day 5 | 1.95 ng/mL | Standard Deviation 2.38 |
Secondary
Percent Change From Baseline in Gastric Emptying (GE) Time as Measured by the SmartPill on Day 7 for Part 1
SmartPill is an ingestible capsule that measures pressure, potential of hydrogen (pH) and temperature as it travels through the gastrointestinal (GI) tract to assess GE and GI motility. SmartPill eliminates radiation exposure and is the only motility test that provides a complete transit profile of the GI tract.
Time frame: Baseline and Day 7
Population: FAS included all participants who were randomized (Part 1), received at least 1 dose of study drug, had a baseline value, and had at least 1 valid postbaseline value for assessment of at least one of the PD measurements. Overall number of participants analyzed is number of participants with evaluable data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Placebo | Percent Change From Baseline in Gastric Emptying (GE) Time as Measured by the SmartPill on Day 7 for Part 1 | 124.62 percent change in GE time | Standard Deviation 181.125 |
| Part 1: TAK 906 Maleate 5 mg | Percent Change From Baseline in Gastric Emptying (GE) Time as Measured by the SmartPill on Day 7 for Part 1 | 61.72 percent change in GE time | Standard Deviation 195.867 |
| Part 1: TAK 906 Maleate 25 mg | Percent Change From Baseline in Gastric Emptying (GE) Time as Measured by the SmartPill on Day 7 for Part 1 | 419.27 percent change in GE time | Standard Deviation 885.362 |
| Part 1: TAK 906 Maleate 100 mg | Percent Change From Baseline in Gastric Emptying (GE) Time as Measured by the SmartPill on Day 7 for Part 1 | 71.09 percent change in GE time | Standard Deviation 121.584 |
Comparison: Percent Change in GE time measured by the SmartPill on Day 7 in Part 1.p-value: 0.27495% CI: [-307.58, 13.56]Wilcoxon Rank Sum tests
Comparison: Percent Change in GE time measured by the SmartPill on Day 7 in Part 1.p-value: 0.48195% CI: [-229.73, 530.49]Wilcoxon Rank Sum tests
Comparison: Percent Change in GE on time measured by the SmartPill Day 7 in Part 1.p-value: 0.38295% CI: [-225.87, 98.91]Wilcoxon Rank Sum tests
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 in Part 1
Time frame: Part 1: Day 1 predose and at multiple timepoints, (Up to 8 hours) postdose and Day 7 predose and at multiple timepoints (Up to 48 hours) postdose
Population: PK set included participants who were randomized and received at least 1 dose of study drug and had at least 1 measurable plasma TAK-906 concentration. Overall number of participants analyzed are participants with data available for analysis of Tmax. Number analyzed are participants with evaluable data at given time-point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 in Part 1 | Day 1 | 1.00 hour (hr) |
| Part 1: Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 in Part 1 | Day 7 | 1.00 hour (hr) |
| Part 1: TAK 906 Maleate 5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 in Part 1 | Day 1 | 1.00 hour (hr) |
| Part 1: TAK 906 Maleate 5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 in Part 1 | Day 7 | 1.00 hour (hr) |
| Part 1: TAK 906 Maleate 25 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 in Part 1 | Day 1 | 1.00 hour (hr) |
| Part 1: TAK 906 Maleate 25 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-906 in Part 1 | Day 7 | 0.98 hour (hr) |