A Study to Evaluate the Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) for TAK-906 in Participants With Diabetes Mellitus and Gastroparesis (DG) or With Idiopathic Gastroparesis (IG)
- Conditions
- Diabetes Mellitus and Gastroparesis, Idiopathic Gastroparesis
- Interventions
- Registration Number
- NCT03268941
- Lead Sponsor
- Millennium Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 51
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Placebo TAK-906 Maleate Placebo TAK-906 placebo-matching (4x0 mg), capsule, orally, twice daily (BID) on Days 1-8 and once on Day 9 under fasted conditions. Part 1: TAK 906 Maleate 5 mg TAK-906 Maleate 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. Part 1: TAK 906 Maleate 25 mg TAK-906 Maleate 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. Part 1: TAK 906 Maleate 100 mg TAK-906 Maleate TAK-906 maleate 100 mg (4x25 mg), capsules, orally, BID on Days 1-8 and once a day on Day 9 under fasted conditions. Part 2: TAK-906 Maleate 25 mg Fed Condition TAK-906 Maleate TAK-906 maleate 1x25 mg, capsule, orally, once on Day 1 of Period 1 under fed conditions (high fat breakfast), followed by a minimum 7- day washout. Part 2: TAK-906 Maleate 25 mg Fasted Condition TAK-906 Maleate TAK-906 maleate 1x25 mg, capsule, orally, once on Day 1 of Period 2 under fasted conditions. Part 2: Metoclopramide 10 mg Metaclopramide Metaclopramide 10 mg, tablet, orally, once, 1 hour prior to breakfast on Day 1 in Part 2.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
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 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 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
Trial Locations
- Locations (9)
850 North Kolb Road
🇺🇸Tucson, Arizona, United States
13055 Southwest 42nd Street
🇺🇸Miami, Florida, United States
8200 Southwest 117th Avenue
🇺🇸Miami, Florida, United States
11219 Financial Centre Parkway
🇺🇸Little Rock, Arkansas, United States
9171 West Thunderbird Road
🇺🇸Peoria, Arizona, United States
6035 Shallowford Road
🇺🇸Chattanooga, Tennessee, United States
125 Clairemont Avenue
🇺🇸Decatur, Georgia, United States
616 South Washington Street
🇺🇸Bastrop, Louisiana, United States
26 Stonecreek Circle
🇺🇸Jackson, Tennessee, United States