Type 2 Diabetes Mellitus
Conditions
Keywords
Drug therapy
Brief summary
This is a phase 1, randomized, double-blind, placebo-controlled, 2-center, multiple-dose study in healthy participants and participants with type 2 diabetes mellitus (T2DM). This study will evaluate the safety, tolerability and pharmacokinetics (PK) of TAK-648 when administered as multiple oral doses of TAK-648 solution at escalating dose levels in healthy participants of Japanese decent and participants with T2DM.
Detailed description
The drug being evaluated in this study is TAK-648 for the treatment of T2DM. This study will consist of 2 parts: (1) multiple ascending doses in participants with T2DM treated with a stable dose of metformin, (2) multiple ascending doses in healthy participants of Japanese descent. Part 1 of this study will consist of 2 multiple dose treatment cohorts (Cohorts 1-2 designated as P1C1 and P1C2) dosed sequentially in escalating order. The projected doses of TAK-648 for Part 1 are 0.15 and 0.35 mg of TAK-648, but may be adjusted higher or lower, and additional cohorts may be added, based on available safety and pharmacokinetic (PK) data. All cohorts in Part 1 will consist of 8 (2 placebo) T2DM participants. Part 2 of this study will consist of 3 multiple dose treatment cohorts (Cohorts 1-3 designated as P2C1, P2C2 and P2C3) in healthy participants of Japanese descent dosed sequentially in escalating order. The projected doses of TAK-648 chosen for Part 2 are 0.05, 0.15 and 0.35 mg of TAK-648, but may be adjusted higher or lower based on available safety and PK data. All cohorts in Part 2 will consist of 8 (2 placebo) healthy participants of Japanese descent. Additional cohorts may be recruited and studied as necessary to better evaluate safety, tolerability, PK, and/or PD parameters.
Interventions
DRUGTAK-648
TAK-648 solution
DRUGPlacebo
TAK-648 placebo-matching solution
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Part 1: 1. Is an adult male or female and has a historical diagnosis of type 2 diabetes mellitus (T2DM) disease. 2. Is aged 18 to 65 years, inclusive, at the time of informed consent and first study medication dose. 3. Weighs at least 55 kg and has a body mass index (BMI) ≥23.0 kg/m\^2 and ≤35.0 kg/m\^2 at Screening. 4. Has a systolic blood pressure \>90 and ≤150 mm Hg and a diastolic blood pressure of \>60 and ≤90 mm Hg at Screening and at Check-in (Day -2). If out of range, may be repeated once for eligibility determination within a maximum of5 minutes. 5. Has a calculated creatinine clearance \>60 mL/min at Screening and Check-in (Day -2). 6. Has been treated for inadequate glycemic control with a stable dose of metformin for the least 8 weeks prior to Screening. 7. Has a glycosylated hemoglobin (HbA1c) level between 6.5% and 10.0%, inclusive at Check-in (Day -2). 8. Has a fasting C-peptide concentration ≥0.8 ng/mL at Screening. 9. Has no medical history of type 1 diabetes mellitus (T1DM), hypoglycemia unawareness, diabetic ketoacidosis or hyperosmolar coma. Part 2: 1. Is a healthy adult male or female of Japanese descent (born to Japanese parents and grandparents) and have lived outside of Japan for less than 5 years, inclusive. 2. Is aged 20 to 55 years, inclusive, at the time of informed consent and first study medication dose. 3. Weighs at least 45 kg and has a BMI from 17.0 to 25.0 kg/m\^2, inclusive at Screening. 4. Has a systolic blood pressure \>90 and ≤150 mm Hg and a diastolic blood pressure of \>60 and ≤90 mm Hg at Screening and at Check-in (Day -2). If out of range, may be repeated once for eligibility determination within a maximum of 5 minutes. 5. Has a calculated creatinine clearance \>60 mL/min at Screening and Check-in (Day -2).
Exclusion criteria
Part 1: 1. Has Screening or Check-in (Day -2) laboratory values of serum creatinine ≥1.5 mg/dL for males or ≥1.4 mg/dL \[females\] or abnormal creatinine clearance. 2. Has a history of T1DM, hypoglycemia unawareness, diabetic ketoacidosis, or hyperosmolar coma. 3. Has a history of any clinically significant retinopathy, which is defined as more than moderate nonproliferative diabetic retinopathy or any stage of proliferative diabetic retinopathy or any history of laser-treated retinopathy. 4. Has received any antihyperglycemic medication with the exception of metformin within the previous 12 weeks of Check-in (Day -2) or the subject has changed the dose of metformin within the previous 8 weeks of Screening. 5. Is expecting to receive, receiving or has received systemic glucocorticoid therapy for a duration longer than 5 days within the previous 12 weeks of Check-in (Day -2). Parts 1 and 2: 1. Has received any investigational compound within 30 days prior to the first dose of study medication. 2. Has received TAK-648 in a previous clinical study or as a therapeutic agent. 3. Has any significant medical histories or currently uncontrolled clinical conditions, which may not be safe for participants to participate in the study, may impact the ability of the participant to participate in the study, or may potentially confound the study results. The concerned significant medical histories and uncontrolled clinical conditions include (may not be limited to) cardiovascular (such as ischemic heart disease, heart failure, cardiomyopathy, clinically significant arrhythmia, uncontrolled or unstable blood pressure), central nervous system, hepatic or hematopoietic disease(s), renal dysfunction, metabolic or endocrine dysfunction, pulmonary diseases including serious allergy and asthma hypoxemia, seizures, or allergic skin rash. 4. Has a history of significant GI disorders manifested with persistent, chronic or intermittent nausea, vomiting or diarrhea, or has a current or recent (within 6 months) GI disease that would influence the absorption of drugs (eg, a history or malabsorption, severe esophageal reflux, peptic ulcer disease or erosive esophagitis with frequent \[more than once per week\] occurrence of heartburn). 5. Has diagnosis of major depression, bipolar disorder or anxiety disorders, or has a risk of anxiety, depression, or insomnia according to the investigator's clinical judgment per HAM-D17 at Screening or has received any medication to treat any psychological disorders within 1 year. 6. Has a risk of suicide according to the investigator's clinical judgment per C-SSRS at Screening or has made a suicide attempt in the past 6 months prior to Screening. 7. Has a known hypersensitivity to any component of the formulation ofTAK-648, or to a PDE4 inhibitor (eg, roflumilast) or Listerine strips. 8. Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -2). 9. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. 10. Has taken any excluded medication, supplements, or food products. 11. If female, is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during such time period. 12. If male, intends to donate sperm during the course of this study or for 12 weeks thereafter. 13. Has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1. 14. Has a positive test result for HBsAg, anti-HCV, at Screening or a known history of human immunodeficiency virus infection. 15. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 6 weeks prior to Check-in (Day -2). Cotinine test is positive at Screening or Check-in (Day -2). 16. Has poor peripheral venous access. 17. Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 30 days prior to Day 1. 18. Has a Screening or Check-in (Day -2) abnormal (clinically significant) ECG, including but not limited to those with evidence of prolonged QT/QTc interval at Baseline (eg, QTc interval \>450 milliseconds) or those at risk for QT prolongation (eg with a family history of long QT syndrome). Entry of any subject with an abnormal (not clinically significant) ECG must be approved, and documented by signature by the principal investigator or medically qualified subinvestigator. 19. Has abnormal Screening or Check-in (Day -2) laboratory values that suggest a clinically significant underlying disease or participant with the following laboratory abnormalities: ALT and/or AST \>2.5×ULN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 1 | Up to Day 34 | 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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
| Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2 | Up to Day 26 | 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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
| Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 1 | Up to Day 20 | — |
| Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2 | Up to Day 13 | — |
| Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 1 | Up to Day 20 | Vital signs included body temperature (oral), sitting blood pressure (after 5 minutes resting), respiration rate and pulse (bpm). |
| Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 | Up to Day 13 | Vital signs included body temperature (oral), sitting blood pressure (after 5 minutes resting), respiration rate and pulse (bpm), |
| Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 1 | Up to Day 20 | Severe hypoglycemia was defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. |
| Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 2 | Up to Day 13 | Severe hypoglycemia was defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. |
Secondary
| Measure | Time frame |
|---|---|
| AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 1 | Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours) |
| Cmax: Maximum Plasma Concentration for TAK-648 for Part 1 | Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours) |
| AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2 | Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours) |
| Cmax: Maximum Plasma Concentration for TAK-648 for Part 2 | Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours) |
| Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 1 | Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours) |
| Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2 | Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours) |
| AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 1 | Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours) |
| AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 2 | Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours) |
| AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 1 | Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours) |
| AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2 | Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours) |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 2 investigative sites in the United States from 02 April 2015 to 04 November 2015.
Pre-assignment details
Participants with a diagnosis of Type 2 Diabetes Mellitus (T2DM) were enrolled in 1 of 3 treatment groups: placebo, 0.35 mg or 0.80 mg TAK-648 in Part 1. Healthy Japanese volunteers were enrolled in 1 of 5 treatment groups: placebo, 0.05 mg, 0.15 mg, 0.35 mg or 0.80 mg TAK-648 in Part 2.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg Participants with T2DM in study Part 1, Cohort 1 received TAK-648 0.35 mg, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by once daily (QD) doses starting on Day 4 and continuing through Day 17 (14 days). | 6 |
| Part 1 Cohort 2: TAK-648 0.80 mg Participants with T2DM in study Part 1, Cohort 2 received TAK-648 0.80 mg, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by once daily (QD) doses starting on Day 4 and continuing through Day 17 (14 days). | 6 |
| Part 1: Placebo Cohort 1-2 Participants with T2DM in study Part 1 received placebo-matching TAK-648, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by once daily (QD) doses starting on Day 4 and continuing through Day 17 (14 days). | 4 |
| Part 2 Cohort 1: TAK-648 0.05 mg Healthy participants of Japanese descent in study Part 2, Cohort 1 received TAK-648 0.05 mg, solution , orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by multiple QD doses starting on Day 4 and continuing through Day 10 (7 days). | 6 |
| Part 2 Cohort 2: TAK-648 0.15 mg Healthy participants of Japanese descent in study Part 2, Cohort 2 received TAK-648 0.15 mg, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by multiple QD doses starting on Day 4 and continuing through Day 10 (7 days). | 6 |
| Part 2 Cohort 3: TAK-648 0.35 mg Healthy participants of Japanese descent in study Part 2, Cohort 3 received TAK-648 0.35 mg, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by multiple QD doses starting on Day 4 and continuing through Day 10 (7 days). | 6 |
| Part 2 Cohort 4: TAK-648 0.80 mg Healthy participants of Japanese descent in study Part 2, Cohort 4 received TAK-648 0.80 mg, solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by multiple QD doses starting on Day 4 and continuing through Day 10 (7 days). | 6 |
| Part 2: Placebo Cohort 1-4 Healthy participants of Japanese descent in study Part 2, received TAK-648 placebo-matching solution, orally, single dose on Day 1, no drug administration on Days 2 to 3, followed by multiple QD doses starting on Day 4 and continuing through Day 10 (7 days). | 8 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Part 2 | Other Reason Not Specified | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part 2 | Voluntary Withdrawal | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1 Cohort 1: TAK-648 0.35 mg | Part 1 Cohort 2: TAK-648 0.80 mg | Part 1: Placebo Cohort 1-2 | Part 2 Cohort 1: TAK-648 0.05 mg | Part 2 Cohort 2: TAK-648 0.15 mg | Part 2 Cohort 3: TAK-648 0.35 mg | Part 2 Cohort 4: TAK-648 0.80 mg | Part 2: Placebo Cohort 1-4 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | NA years | NA years | NA years | 37.3 years STANDARD_DEVIATION 9.63 | 36.0 years STANDARD_DEVIATION 10.45 | 32.2 years STANDARD_DEVIATION 12.48 | 33.0 years STANDARD_DEVIATION 4.1 | 35.3 years STANDARD_DEVIATION 9.82 | 34.8 years STANDARD_DEVIATION 9.26 |
| Body Mass Index (BMI) | 31.12 kg/m^2 STANDARD_DEVIATION 2.176 | 29.12 kg/m^2 STANDARD_DEVIATION 4.599 | 30.00 kg/m^2 STANDARD_DEVIATION 4.146 | NA kg/m^2 | NA kg/m^2 | NA kg/m^2 | NA kg/m^2 | NA kg/m^2 | 22.16 kg/m^2 STANDARD_DEVIATION 2.072 |
| Duration of Type 2 Diabetes Mellitus (T2DM) | 12.7 years STANDARD_DEVIATION 5.68 | 9.3 years STANDARD_DEVIATION 5.16 | 9.0 years STANDARD_DEVIATION 3.37 | NA years | NA years | NA years | NA years | NA years | 10.5 years STANDARD_DEVIATION 4.99 |
| Height | NA cm | NA cm | NA cm | 172.7 cm STANDARD_DEVIATION 5.32 | 169.0 cm STANDARD_DEVIATION 13.02 | 164.5 cm STANDARD_DEVIATION 6.57 | 166.3 cm STANDARD_DEVIATION 8.19 | 164.9 cm STANDARD_DEVIATION 8.43 | 165.6 cm STANDARD_DEVIATION 9.75 |
| Metformin Dose | 1425.0 mg STANDARD_DEVIATION 534.56 | 1400.0 mg STANDARD_DEVIATION 709.93 | 1812.5 mg STANDARD_DEVIATION 645.98 | NA mg | NA mg | NA mg | NA mg | NA mg | 1512.5 mg STANDARD_DEVIATION 615.49 |
| Race/Ethnicity, Customized Asian | NA participants 534.56 | NA participants 709.93 | NA participants 645.98 | 6 participants | 6 participants | 6 participants | 6 participants | 8 participants | NA participants |
| Race/Ethnicity, Customized Hispanic or Latino | 6 participants 4.09 | 5 participants 9.95 | 4 participants 8.7 | NA participants | NA participants | NA participants | NA participants | NA participants | NA participants |
| Race/Ethnicity, Customized Non-Hispanic and Latino | 0 participants | 1 participants | 0 participants | NA participants | NA participants | NA participants | NA participants | NA participants | NA participants |
| Race/Ethnicity, Customized White | 6 participants 2.176 | 6 participants 4.599 | 4 participants 4.146 | NA participants | NA participants | NA participants | NA participants | NA participants | NA participants |
| Region of Enrollment United States | NA participants | NA participants | NA participants | 6 participants 9.63 | 6 participants 10.45 | 6 participants 12.48 | 6 participants 4.1 | 8 participants 9.82 | NA participants |
| Sex: Female, Male Female | NA Participants | NA Participants | NA Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 5 Participants | NA Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 0 Participants | NA Participants | NA Participants | NA Participants | NA Participants | NA Participants | NA Participants |
| Weight | 91.45 kg STANDARD_DEVIATION 5.082 | 81.22 kg STANDARD_DEVIATION 17.359 | 73.38 kg STANDARD_DEVIATION 17.068 | NA kg | NA kg | NA kg | NA kg | NA kg | 83.09 kg STANDARD_DEVIATION 14.895 |
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 | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 6 | 2 / 6 | 4 / 4 | 6 / 6 | 2 / 6 | 4 / 6 | 5 / 6 | 3 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 1
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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Up to Day 34
Population: Safety Analysis Set included of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 1 | 83.3 percentage of participants |
| Part 1 Cohort 2: TAK-648 0.80 mg | Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 1 | 33.3 percentage of participants |
| Part 1: Placebo Cohort 1-2 | Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 1 | 100.0 percentage of participants |
Primary
Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2
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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Up to Day 26
Population: Safety Analysis Set included of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2 | 100.0 percentage of participants |
| Part 1 Cohort 2: TAK-648 0.80 mg | Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2 | 33.3 percentage of participants |
| Part 1: Placebo Cohort 1-2 | Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2 | 66.7 percentage of participants |
| Part 2 Cohort 4: TAK-648 0.80 mg | Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2 | 83.3 percentage of participants |
| Part 2: Placebo Cohort 1-4 | Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2 | 37.5 percentage of participants |
Primary
Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 1
Severe hypoglycemia was defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
Time frame: Up to Day 20
Population: Safety Analysis Set included of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 1 | 0 percentage of participants |
| Part 1 Cohort 2: TAK-648 0.80 mg | Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 1 | 0 percentage of participants |
| Part 1: Placebo Cohort 1-2 | Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 1 | 0 percentage of participants |
Primary
Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 2
Severe hypoglycemia was defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
Time frame: Up to Day 13
Population: Safety Analysis Set included of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 2 | 0 percentage of participants |
| Part 1 Cohort 2: TAK-648 0.80 mg | Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 2 | 0 percentage of participants |
| Part 1: Placebo Cohort 1-2 | Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 2 | 0 percentage of participants |
| Part 2 Cohort 4: TAK-648 0.80 mg | Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 2 | 0 percentage of participants |
| Part 2: Placebo Cohort 1-4 | Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 2 | 0 percentage of participants |
Primary
Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 1
Time frame: Up to Day 20
Population: Safety Analysis Set included of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 1 | 0 percentage of participants |
| Part 1 Cohort 2: TAK-648 0.80 mg | Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 1 | 0 percentage of participants |
| Part 1: Placebo Cohort 1-2 | Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 1 | 0 percentage of participants |
Primary
Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2
Time frame: Up to Day 13
Population: Safety Analysis Set included of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2 | 0 percentage of participants |
| Part 1 Cohort 2: TAK-648 0.80 mg | Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2 | 0 percentage of participants |
| Part 1: Placebo Cohort 1-2 | Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2 | 0 percentage of participants |
| Part 2 Cohort 4: TAK-648 0.80 mg | Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2 | 0 percentage of participants |
| Part 2: Placebo Cohort 1-4 | Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2 | 0 percentage of participants |
Primary
Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 1
Vital signs included body temperature (oral), sitting blood pressure (after 5 minutes resting), respiration rate and pulse (bpm).
Time frame: Up to Day 20
Population: Safety Analysis Set included of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 1 | < Lower Criteria | 0 percentage of participants |
| Part 1 Cohort 1: TAK-648 0.35 mg | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 1 | > Upper Criteria | 16.7 percentage of participants |
| Part 1 Cohort 2: TAK-648 0.80 mg | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 1 | < Lower Criteria | 16.7 percentage of participants |
| Part 1 Cohort 2: TAK-648 0.80 mg | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 1 | > Upper Criteria | 0 percentage of participants |
| Part 1: Placebo Cohort 1-2 | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 1 | < Lower Criteria | 50.0 percentage of participants |
| Part 1: Placebo Cohort 1-2 | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 1 | > Upper Criteria | 0 percentage of participants |
Primary
Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2
Vital signs included body temperature (oral), sitting blood pressure (after 5 minutes resting), respiration rate and pulse (bpm),
Time frame: Up to Day 13
Population: Safety Analysis Set included of all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 | < Lower Criteria | 50.0 percentage of participants |
| Part 1 Cohort 1: TAK-648 0.35 mg | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 | > Upper Criteria | 0 percentage of participants |
| Part 1 Cohort 2: TAK-648 0.80 mg | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 | < Lower Criteria | 50.0 percentage of participants |
| Part 1 Cohort 2: TAK-648 0.80 mg | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 | > Upper Criteria | 16.7 percentage of participants |
| Part 1: Placebo Cohort 1-2 | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 | < Lower Criteria | 33.3 percentage of participants |
| Part 1: Placebo Cohort 1-2 | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 | > Upper Criteria | 0 percentage of participants |
| Part 2 Cohort 4: TAK-648 0.80 mg | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 | > Upper Criteria | 0 percentage of participants |
| Part 2 Cohort 4: TAK-648 0.80 mg | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 | < Lower Criteria | 33.3 percentage of participants |
| Part 2: Placebo Cohort 1-4 | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 | < Lower Criteria | 37.5 percentage of participants |
| Part 2: Placebo Cohort 1-4 | Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2 | > Upper Criteria | 0 percentage of participants |
Secondary
AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 1
Time frame: Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours)
Population: The PK Set included all participants in the safety set with at least 1 measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 1 | Day 1 | 31.973 ng*hr/mL | Standard Deviation 10.3893 |
| Part 1 Cohort 1: TAK-648 0.35 mg | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 1 | Day 17 | 46.827 ng*hr/mL | Standard Deviation 21.8685 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 1 | Day 1 | 89.043 ng*hr/mL | Standard Deviation 29.063 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 1 | Day 17 | 110.882 ng*hr/mL | Standard Deviation 41.8979 |
Secondary
AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2
Time frame: Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours)
Population: The PK Set included all participants in the safety set with at least 1 measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2 | Day 1 | 5.147 ng*hr/mL | Standard Deviation 1.3861 |
| Part 1 Cohort 1: TAK-648 0.35 mg | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2 | Day 10 | 5.538 ng*hr/mL | Standard Deviation 1.5656 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2 | Day 10 | 19.922 ng*hr/mL | Standard Deviation 3.8508 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2 | Day 1 | 15.078 ng*hr/mL | Standard Deviation 3.0768 |
| Part 1: Placebo Cohort 1-2 | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2 | Day 1 | 39.160 ng*hr/mL | Standard Deviation 12.8099 |
| Part 1: Placebo Cohort 1-2 | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2 | Day 10 | 39.103 ng*hr/mL | Standard Deviation 14.5245 |
| Part 2 Cohort 4: TAK-648 0.80 mg | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2 | Day 1 | 64.694 ng*hr/mL | Standard Deviation 20.2316 |
| Part 2 Cohort 4: TAK-648 0.80 mg | AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2 | Day 10 | 77.369 ng*hr/mL | Standard Deviation 36.7414 |
Secondary
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 1
Time frame: Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours)
Population: The PK Set included all participants in the safety set with at least 1 measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 1 | Day 1 | 31.676 ng*hr/mL | Standard Deviation 10.2111 |
| Part 1 Cohort 1: TAK-648 0.35 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 1 | Day 17 | 43.908 ng*hr/mL | Standard Deviation 18.4433 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 1 | Day 1 | 88.168 ng*hr/mL | Standard Deviation 28.2484 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 1 | Day 17 | 107.492 ng*hr/mL | Standard Deviation 39.621 |
Secondary
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 2
Time frame: Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours)
Population: The PK Set included all participants in the safety set with at least 1 measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 2 | Day 1 | 5.018 ng*hr/mL | Standard Deviation 1.3681 |
| Part 1 Cohort 1: TAK-648 0.35 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 2 | Day 10 | 5.355 ng*hr/mL | Standard Deviation 1.5083 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 2 | Day 10 | 19.274 ng*hr/mL | Standard Deviation 3.5884 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 2 | Day 1 | 14.861 ng*hr/mL | Standard Deviation 3.0267 |
| Part 1: Placebo Cohort 1-2 | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 2 | Day 1 | 38.878 ng*hr/mL | Standard Deviation 12.7876 |
| Part 1: Placebo Cohort 1-2 | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 2 | Day 10 | 38.123 ng*hr/mL | Standard Deviation 14.0762 |
| Part 2 Cohort 4: TAK-648 0.80 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 2 | Day 1 | 63.376 ng*hr/mL | Standard Deviation 19.613 |
| Part 2 Cohort 4: TAK-648 0.80 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-648 for Part 2 | Day 10 | 75.183 ng*hr/mL | Standard Deviation 35.8763 |
Secondary
AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 1
Time frame: Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours)
Population: The PK Set included all participants in the safety set with at least 1 measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 1 | Day 1 | 30.209 ng*hr/mL | Standard Deviation 9.0944 |
| Part 1 Cohort 1: TAK-648 0.35 mg | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 1 | Day 17 | 39.283 ng*hr/mL | Standard Deviation 15.7882 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 1 | Day 1 | 82.148 ng*hr/mL | Standard Deviation 21.9186 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 1 | Day 17 | 95.028 ng*hr/mL | Standard Deviation 28.9547 |
Secondary
AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2
Time frame: Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours)
Population: The PK Set included all participants in the safety set with at least 1 measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2 | Day 1 | 4.833 ng*hr/mL | Standard Deviation 1.2018 |
| Part 1 Cohort 1: TAK-648 0.35 mg | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2 | Day 10 | 5.036 ng*hr/mL | Standard Deviation 1.3032 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2 | Day 10 | 17.215 ng*hr/mL | Standard Deviation 2.8909 |
| Part 1 Cohort 2: TAK-648 0.80 mg | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2 | Day 1 | 13.902 ng*hr/mL | Standard Deviation 2.5432 |
| Part 1: Placebo Cohort 1-2 | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2 | Day 1 | 36.570 ng*hr/mL | Standard Deviation 11.8662 |
| Part 1: Placebo Cohort 1-2 | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2 | Day 10 | 34.661 ng*hr/mL | Standard Deviation 13.0489 |
| Part 2 Cohort 4: TAK-648 0.80 mg | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2 | Day 1 | 59.507 ng*hr/mL | Standard Deviation 18.5291 |
| Part 2 Cohort 4: TAK-648 0.80 mg | AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2 | Day 10 | 67.785 ng*hr/mL | Standard Deviation 28.2776 |
Secondary
Cmax: Maximum Plasma Concentration for TAK-648 for Part 1
Time frame: Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours)
Population: The Pharmacokinetic (PK) Set included all participants in the safety set with at least 1 measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Cmax: Maximum Plasma Concentration for TAK-648 for Part 1 | Day 1 | 6.342 ng/mL | Standard Deviation 1.3552 |
| Part 1 Cohort 1: TAK-648 0.35 mg | Cmax: Maximum Plasma Concentration for TAK-648 for Part 1 | Day 17 | 7.950 ng/mL | Standard Deviation 2.3885 |
| Part 1 Cohort 2: TAK-648 0.80 mg | Cmax: Maximum Plasma Concentration for TAK-648 for Part 1 | Day 1 | 16.150 ng/mL | Standard Deviation 3.2073 |
| Part 1 Cohort 2: TAK-648 0.80 mg | Cmax: Maximum Plasma Concentration for TAK-648 for Part 1 | Day 17 | 16.283 ng/mL | Standard Deviation 4.6521 |
Secondary
Cmax: Maximum Plasma Concentration for TAK-648 for Part 2
Time frame: Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours)
Population: The PK Set included all participants in the safety set with at least 1 measurable plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Cmax: Maximum Plasma Concentration for TAK-648 for Part 2 | Day 1 | 0.764 mg/mL | Standard Deviation 0.2436 |
| Part 1 Cohort 1: TAK-648 0.35 mg | Cmax: Maximum Plasma Concentration for TAK-648 for Part 2 | Day 10 | 0.670 mg/mL | Standard Deviation 0.2054 |
| Part 1 Cohort 2: TAK-648 0.80 mg | Cmax: Maximum Plasma Concentration for TAK-648 for Part 2 | Day 10 | 2.355 mg/mL | Standard Deviation 0.1499 |
| Part 1 Cohort 2: TAK-648 0.80 mg | Cmax: Maximum Plasma Concentration for TAK-648 for Part 2 | Day 1 | 1.955 mg/mL | Standard Deviation 0.3455 |
| Part 1: Placebo Cohort 1-2 | Cmax: Maximum Plasma Concentration for TAK-648 for Part 2 | Day 1 | 5.925 mg/mL | Standard Deviation 1.9491 |
| Part 1: Placebo Cohort 1-2 | Cmax: Maximum Plasma Concentration for TAK-648 for Part 2 | Day 10 | 6.430 mg/mL | Standard Deviation 2.5774 |
| Part 2 Cohort 4: TAK-648 0.80 mg | Cmax: Maximum Plasma Concentration for TAK-648 for Part 2 | Day 1 | 10.080 mg/mL | Standard Deviation 5.2665 |
| Part 2 Cohort 4: TAK-648 0.80 mg | Cmax: Maximum Plasma Concentration for TAK-648 for Part 2 | Day 10 | 9.612 mg/mL | Standard Deviation 3.5611 |
Secondary
Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 1
Time frame: Days 1 and 17 pre-dose and multiple time-points post-dose (Up to 72 hours)
Population: The PK Set included all participants in the safety set with at least 1 measurable plasma concentration.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 1 | Day 1 | 0.500 hours (hr) |
| Part 1 Cohort 1: TAK-648 0.35 mg | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 1 | Day 17 | 0.500 hours (hr) |
| Part 1 Cohort 2: TAK-648 0.80 mg | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 1 | Day 1 | 1.000 hours (hr) |
| Part 1 Cohort 2: TAK-648 0.80 mg | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 1 | Day 17 | 0.710 hours (hr) |
Secondary
Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2
Time frame: Days 1 and 10 pre-dose and multiple time-points post-dose (Up to 72 hours)
Population: The PK Set included all participants in the safety set with at least 1 measurable plasma concentration.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1 Cohort 1: TAK-648 0.35 mg | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2 | Day 1 | 1.000 hr |
| Part 1 Cohort 1: TAK-648 0.35 mg | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2 | Day 10 | 1.500 hr |
| Part 1 Cohort 2: TAK-648 0.80 mg | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2 | Day 10 | 0.750 hr |
| Part 1 Cohort 2: TAK-648 0.80 mg | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2 | Day 1 | 1.000 hr |
| Part 1: Placebo Cohort 1-2 | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2 | Day 1 | 1.000 hr |
| Part 1: Placebo Cohort 1-2 | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2 | Day 10 | 1.000 hr |
| Part 2 Cohort 4: TAK-648 0.80 mg | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2 | Day 1 | 1.000 hr |
| Part 2 Cohort 4: TAK-648 0.80 mg | Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2 | Day 10 | 1.000 hr |