TAK-906

ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD composite score included score of nausea, early satiety, upper abdominal pain, and postprandial fullness. The severity scores of these symptoms range from 0 (none) to 4 (very severe). The daily composite score was calculated by summing the scores on the 4 symptom items (nausea, early satiety, postprandial fullness, and upper abdominal pain) and then dividing by 4, that is the number of items within the composite score. Thus, the maximum daily composite score was (4 symptoms × maximum score 4 divided by 4) = 16/4 = 4. The ANMS GCSI-DD daily composite score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. Mixed-effects Model for Repeated Measures (MMRM) was used for the analysis.

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.

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.

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.

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.

Bioavailability is defined as the proportion of a drug which enters the circulation when introduced into the body and so is able to have an active effect. Percent absolute bioavailability for plasma TAK-906, calculated as geometric least squares mean ratio: \[Actual Dose (IV) x AUC∞ (oral)\] / \[Actual Dose (oral) x AUC∞ (IV)\] multiplied (x) 100, where AUC∞ for IV infusion was normalized to a 50 mg dose.

An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study; it does not necessarily have to have a causal relationship with the treatment or study participation. A treatment-emergent adverse events (TEAE) is defined as an AE whose date of onset occurs on or after the start of study drug.

Reported data were numbers of participants who met markedly abnormal criteria of vital signs. Vital signs included body temperature, respiratory rate, blood pressure, and pulse. Vital signs collected were classified as markedly abnormal values if they met the following criteria: systolic blood pressure less than (\<) 85 millimeter of mercury (mmHg) or greater than (\>) 180 mmHg, diastolic blood pressure \<50 mmHg or \>110 mmHg, pulse \<50 beats per minute (bpm) or \>120 bpm, body temperature \<35.6 °C or \>37.7 °C.

Reported data were numbers of participants who met markedly abnormal criteria of clinical laboratory test results. Clinical laboratory test results collected were classified as markedly abnormal values if they met the following criteria: red blood cells \<0.8×lower limit of normal (LLN) or \>1.2×upper limit of normal (ULN), platelets \<75×10\^3/μL or \>600×10\^3/μL, white blood cells \<0.5×LLN or \>1.5×ULN, protein (total) \<0.8×LLN or \>1.2×ULN, albumin \<2.5 g/dL, blood urea nitrogen \>30 mg/dL, uric acid \>13.0 mg/dL, creatinine \>2.0 mg/dL, total cholesterol \>300 mg/dL, triglycerides \>2.5×ULN, bilirubin (total) \>2.0 mg/dL, Sodium \<130 mEq/L or \>150 mEq/L, Potassium \<3.0 mEq/L or \>6.0 mEq/L, Chloride \<75 mEq/L or \>126 mEq/L, Calcium \<7.0 mg/dL or \>11.5 mg/dL, Phosphorus \<1.6 mg/dL or \>6.2 mg/dL, alkaline phosphatase \>3×ULN, aspartate aminotransferase \>3×ULN, alanine aminotransferase \>3×ULN, gamma-glutamyl transferase \>3×ULN, glucose \<50 mg/dL or \>350 mg/dL, Magnesium \<1.2 mg/dL or \>3.0 mg/dL.

Reported data were numbers of participants who met markedly abnormal criteria of 12-lead ECG. A standard 12-lead ECG was performed. The data collected was classified as markedly abnormal values if it met the following criteria: heart rate \<50 bpm or \>120 bpm, QT interval less than or equal to (\<=) 50 msec or greater than or equal to (\>=) 460 msec, QTcF interval \<=50 msec or either of the following conditions was met: observed value \>=500 msec, change from Day 1 Predose \>= 30 msec and observed value \>=450 msec.

An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study; it does not necessarily have to have a causal relationship with the treatment or study participation. A treatment-emergent adverse events (TEAE) is defined as an AE whose date of onset occurs on or after the start of study drug.