CompletedNCT02430870Updated Aug 31, 2016Results posted

TAK-648 Multiple-Rising Dose Study in Healthy Japanese Participants and Non-Japanese Participants With Type 2 Diabetes Mellitus

A Phase 1 interventional study of TAK-648 and Placebo in Type 2 Diabetes Mellitus, sponsored by Takeda. Completed at 2 sites in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-08-31.

Sponsored by Takeda · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 48
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Type 2 Diabetes Mellitus

Browse trials for

Diabetes Mellitus, Type 2 9,590

Keywords

Drug therapy

In context

Diabetes Mellitus, Type 2

9,590 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,332 are open to participants now.

This study's enrollment of 48 is below the median of 81 across 7,713 interventional studies indexed under Diabetes Mellitus, Type 2.

Browse Diabetes Mellitus, Type 2 studies →

Lead sponsor

Takeda is the lead sponsor of 1,025 studies on the registry; 91 are open to participants now.

Of its 177 completed or terminated interventional studies of FDA-regulated products, 153 (86%) have results posted.

Browse Takeda studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Part 1:

Is an adult male or female and has a historical diagnosis of type 2 diabetes mellitus (T2DM) disease.
Is aged 18 to 65 years, inclusive, at the time of informed consent and first study medication dose.
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.
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.
Has a calculated creatinine clearance >60 mL/min at Screening and Check-in (Day -2).
Has been treated for inadequate glycemic control with a stable dose of metformin for the least 8 weeks prior to Screening.
Has a glycosylated hemoglobin (HbA1c) level between 6.5% and 10.0%, inclusive at Check-in (Day -2).
Has a fasting C-peptide concentration ≥0.8 ng/mL at Screening.
Has no medical history of type 1 diabetes mellitus (T1DM), hypoglycemia unawareness, diabetic ketoacidosis or hyperosmolar coma.

Part 2:

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.
Is aged 20 to 55 years, inclusive, at the time of informed consent and first study medication dose.
Weighs at least 45 kg and has a BMI from 17.0 to 25.0 kg/m\^2, inclusive at Screening.
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.
Has a calculated creatinine clearance >60 mL/min at Screening and Check-in (Day -2).

Exclusion criteria

Exclusion Criteria:

Part 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.
Has a history of T1DM, hypoglycemia unawareness, diabetic ketoacidosis, or hyperosmolar coma.
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.
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.
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:

Has received any investigational compound within 30 days prior to the first dose of study medication.
Has received TAK-648 in a previous clinical study or as a therapeutic agent.
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.
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).
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.
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.
Has a known hypersensitivity to any component of the formulation ofTAK-648, or to a PDE4 inhibitor (eg, roflumilast) or Listerine strips.
Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -2).
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.
Has taken any excluded medication, supplements, or food products.
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.
If male, intends to donate sperm during the course of this study or for 12 weeks thereafter.
Has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1.
Has a positive test result for HBsAg, anti-HCV, at Screening or a known history of human immunodeficiency virus infection.
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).
Has poor peripheral venous access.
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.
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.
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.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 48 participants (actual)

Study arms

Experimental
Part 1 Cohort 1: TAK-648 0.35 mg
Participants with T2DM on a stable dose of metformin 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).
Drug: TAK-648
Experimental
Part 1 Cohort 2: TAK-648 0.80 mg
Participants with T2DM on a stable dose of metformin 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).
Drug: TAK-648
Placebo comparator
Part 1: Placebo Cohort 1-2
Participants with T2DM on a stable dose of metformin 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).
Drug: Placebo
Experimental
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).
Drug: TAK-648
Experimental
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).
Drug: TAK-648
Experimental
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).
Drug: TAK-648
Experimental
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).
Drug: TAK-648
Placebo comparator
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).
Drug: Placebo

Interventions

DrugTAK-648
TAK-648 solution
DrugPlacebo
TAK-648 placebo-matching solution

What researchers measure

Primary outcomes

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
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
Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 1
Time frame: Up to Day 20
Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2
Time frame: Up to Day 13
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
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
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
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

Secondary outcomes

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)
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)
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)
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)
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)
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)
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)
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)
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)
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)

Results

Posted Aug 31, 2016

Participant flow

Participants took part in the study at 2 investigative sites in the United States from 02 April 2015 to 04 November 2015.

Part 1

Participant flow — Part 1
Milestone	Part 1 Cohort 1: TAK-648 0.35 mg	Part 1 Cohort 2: TAK-648 0.80 mg	Part 1: Placebo Cohort 1-2
Started	6	6	4
Completed	6	6	4
Not completed	0	0	0

Part 2

Participant flow — Part 2
Milestone	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
Started	6	6	6	6	8
Completed	6	6	6	5	7
Not completed	0	0	0	1	1
Withdrew: Voluntary withdrawal	0	0	0	1	0
Withdrew: Other reason not specified	0	0	0	0	1

Outcome measures

PrimaryPercentage 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
Reported as:: Number · percentage of participants

Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 1
percentage of participants	Part 1 Cohort 1: TAK-648 0.35 mg	Part 1 Cohort 2: TAK-648 0.80 mg	Part 1: Placebo Cohort 1-2
Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 1	83.3	33.3	100.0

PrimaryPercentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2

Time frame:: Up to Day 26
Reported as:: Number · percentage of participants

Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2
percentage of participants	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
Percentage of Participants Who Have at Least 1 Treatment-Emergent Adverse Event (TEAE) for Part 2	100.0	33.3	66.7	83.3	37.5

PrimaryPercentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 1

Time frame:: Up to Day 20
Reported as:: Number · percentage of participants

Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 1
percentage of participants	Part 1 Cohort 1: TAK-648 0.35 mg	Part 1 Cohort 2: TAK-648 0.80 mg	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	0	0

PrimaryPercentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2

Time frame:: Up to Day 13
Reported as:: Number · percentage of participants

Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2
percentage of participants	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
Percentage of Participants With Markedly Abnormal Laboratory Values at Least Once Post-dose During Dosing for Part 2	0	0	0	0	0

PrimaryPercentage 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
Reported as:: Number · percentage of participants

Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 1
percentage of participants	Part 1 Cohort 1: TAK-648 0.35 mg	Part 1 Cohort 2: TAK-648 0.80 mg	Part 1: Placebo Cohort 1-2
< Lower Criteria	0	16.7	50.0
> Upper Criteria	16.7	0	0

PrimaryPercentage 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
Reported as:: Number · percentage of participants

Percentage of Participants With Markedly Abnormal Vital Sign Values at Least Once Post-dose During Dosing for Part 2
percentage of participants	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
< Lower Criteria	50.0	50.0	33.3	33.3	37.5
> Upper Criteria	0	16.7	0	0	0

PrimaryPercentage 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
Reported as:: Number · percentage of participants

Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 1
percentage of participants	Part 1 Cohort 1: TAK-648 0.35 mg	Part 1 Cohort 2: TAK-648 0.80 mg	Part 1: Placebo Cohort 1-2
Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 1	0	0	0

PrimaryPercentage 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
Reported as:: Number · percentage of participants

Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 2
percentage of participants	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
Percentage of Participants Who Have Severe Hypoglycemia at Least Once Post-dose During Dosing For Part 2	0	0	0	0	0

SecondaryCmax: 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)
Reported as:: Mean · ng/mL

Cmax: Maximum Plasma Concentration for TAK-648 for Part 1
ng/mL	Part 1 Cohort 1: TAK-648 0.35 mg	Part 1 Cohort 2: TAK-648 0.80 mg
Day 1	6.342 ± 1.3552	16.150 ± 3.2073
Day 17	7.950 ± 2.3885	16.283 ± 4.6521

SecondaryCmax: 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)
Reported as:: Mean · mg/mL

Cmax: Maximum Plasma Concentration for TAK-648 for Part 2
mg/mL	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
Day 1	0.764 ± 0.2436	1.955 ± 0.3455	5.925 ± 1.9491	10.080 ± 5.2665
Day 10	0.670 ± 0.2054	2.355 ± 0.1499	6.430 ± 2.5774	9.612 ± 3.5611

SecondaryTmax: 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)
Reported as:: Median · hours (hr)

Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 1
hours (hr)	Part 1 Cohort 1: TAK-648 0.35 mg	Part 1 Cohort 2: TAK-648 0.80 mg
Day 1	0.500 (0.50 to 0.50)	1.000 (0.50 to 1.50)
Day 17	0.500 (0.50 to 1.00)	0.710 (0.50 to 2.00)

SecondaryTmax: 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)
Reported as:: Median · hr

Tmax: Time to Reach Maximum Plasma Concentration (Tmax) for TAK-648 for Part 2
hr	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
Day 1	1.000 (0.50 to 2.00)	1.000 (0.50 to 1.50)	1.000 (0.50 to 1.00)	1.000 (0.50 to 1.50)
Day 10	1.500 (1.00 to 2.00)	0.750 (0.50 to 1.50)	1.000 (0.50 to 1.50)	1.000 (0.50 to 4.00)

SecondaryAUClast: 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)
Reported as:: Mean · ng*hr/mL

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
ng*hr/mL	Part 1 Cohort 1: TAK-648 0.35 mg	Part 1 Cohort 2: TAK-648 0.80 mg
Day 1	31.676 ± 10.2111	88.168 ± 28.2484
Day 17	43.908 ± 18.4433	107.492 ± 39.6210

SecondaryAUClast: 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)
Reported as:: Mean · ng*hr/mL

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
ng*hr/mL	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
Day 1	5.018 ± 1.3681	14.861 ± 3.0267	38.878 ± 12.7876	63.376 ± 19.6130
Day 10	5.355 ± 1.5083	19.274 ± 3.5884	38.123 ± 14.0762	75.183 ± 35.8763

SecondaryAUC∞: 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)
Reported as:: Mean · ng*hr/mL

AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 1
ng*hr/mL	Part 1 Cohort 1: TAK-648 0.35 mg	Part 1 Cohort 2: TAK-648 0.80 mg
Day 1	31.973 ± 10.3893	89.043 ± 29.0630
Day 17	46.827 ± 21.8685	110.882 ± 41.8979

SecondaryAUC∞: 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)
Reported as:: Mean · ng*hr/mL

AUC∞: Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for TAK-648 for Part 2
ng*hr/mL	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
Day 1	5.147 ± 1.3861	15.078 ± 3.0768	39.160 ± 12.8099	64.694 ± 20.2316
Day 10	5.538 ± 1.5656	19.922 ± 3.8508	39.103 ± 14.5245	77.369 ± 36.7414

SecondaryAUCtau: 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)
Reported as:: Mean · ng*hr/mL

AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 1
ng*hr/mL	Part 1 Cohort 1: TAK-648 0.35 mg	Part 1 Cohort 2: TAK-648 0.80 mg
Day 1	30.209 ± 9.0944	82.148 ± 21.9186
Day 17	39.283 ± 15.7882	95.028 ± 28.9547

SecondaryAUCtau: 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)
Reported as:: Mean · ng*hr/mL

AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 Over the Dosing Interval for TAK-648 for Part 2
ng*hr/mL	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
Day 1	4.833 ± 1.2018	13.902 ± 2.5432	36.570 ± 11.8662	59.507 ± 18.5291
Day 10	5.036 ± 1.3032	17.215 ± 2.8909	34.661 ± 13.0489	67.785 ± 28.2776

Adverse events

Collected over AEs were routinely collected from the time of first study drug administration until Follow-up Visit on Day 34 (±2) days (Part 1), and Day 26 (±2) days (Part 2).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part 1 Cohort 1: TAK-648 0.35 mg	—	0/6 (0%)	5/6 (83.3%)
Part 1 Cohort 2: TAK-648 0.80 mg	—	0/6 (0%)	2/6 (33.3%)
Part 1: Placebo Cohort 1-2	—	0/4 (0%)	4/4 (100%)
Part 2 Cohort 1: TAK-648 0.05 mg	—	0/6 (0%)	6/6 (100%)
Part 2 Cohort 2: TAK-648 0.15 mg	—	0/6 (0%)	2/6 (33.3%)
Part 2 Cohort 3: TAK-648 0.35 mg	—	0/6 (0%)	4/6 (66.7%)
Part 2 Cohort 4: TAK-648 0.80 mg	—	0/6 (0%)	5/6 (83.3%)
Part 2: Placebo Cohort 1-4	—	0/8 (0%)	3/8 (37.5%)

Most frequent other events

Showing 10 of 25

Most frequent other events
Event	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
ConstipationGastrointestinal disorders	0/6	0/6	0/4	0/6	1/6	4/6	3/6	2/8
ErythemaSkin and subcutaneous tissue disorders	4/6	1/6	1/4	1/6	0/6	0/6	0/6	1/8
Application site erythemaGeneral disorders	0/6	0/6	0/4	3/6	0/6	0/6	0/6	0/8
DiarrheaGastrointestinal disorders	0/6	1/6	1/4	0/6	0/6	0/6	0/6	1/8
Abdominal painGastrointestinal disorders	0/6	0/6	1/4	0/6	0/6	0/6	0/6	0/8
NauseaGastrointestinal disorders	0/6	0/6	1/4	0/6	0/6	0/6	0/6	0/8
Application site dermatitisGeneral disorders	0/6	0/6	1/4	0/6	0/6	0/6	0/6	0/8
FatigueGeneral disorders	0/6	0/6	1/4	0/6	0/6	0/6	0/6	0/8
Body tineaInfections and infestations	0/6	0/6	1/4	0/6	0/6	0/6	0/6	0/8
Blood pressure orthostatic decreasedInvestigations	0/6	0/6	1/4	0/6	0/6	0/6	0/6	0/8

Baseline characteristics

Randomized Set included all randomized participants.

Age, Continuous
Age, Continuous(years)	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
Mean	55.3 ± 8.04	55.0 ± 7.01	54.5 ± 7.77	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA ± NA	55.0 ± 7.08

Age, Continuous
Age, Continuous(years)	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
Mean	NA ± NA	NA ± NA	NA ± NA	37.3 ± 9.63	36.0 ± 10.45	32.2 ± 12.48	33.0 ± 4.10	35.3 ± 9.82	34.8 ± 9.26

Sex: Female, Male
Sex: Female, Male(Participants)	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
Female	0	3	4	NA	NA	NA	NA	NA	NA
Male	6	3	0	NA	NA	NA	NA	NA	NA

Sex: Female, Male
Sex: Female, Male(Participants)	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
Female	NA	NA	NA	1	3	3	3	5	NA
Male	NA	NA	NA	5	3	3	3	3	NA

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	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
Hispanic or Latino	6 ± 4.09	5 ± 9.95	4 ± 8.70	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA
Non-Hispanic and Latino	0	1	0	NA	NA	NA	NA	NA	NA

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	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
Non-Hispanic and Latino	NA ± 5.082	NA ± 17.359	NA ± 17.068	6 ± NA	6 ± NA	6 ± NA	6 ± NA	8 ± NA	NA

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	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
White	6 ± 2.176	6 ± 4.599	4 ± 4.146	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	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
Asian	NA ± 534.56	NA ± 709.93	NA ± 645.98	6 ± NA	6 ± NA	6 ± NA	6 ± NA	8 ± NA	NA

10 further baseline measures are reported on the registry.

Study locations

2 sites

Anaheim, California, United States
Chula Vista, California, United States

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Apr 2015, a primary completion of Sep 2015 and a completion of Nov 2015. It does not say whether these dates are actual or estimated.

Results were first posted in Aug 2016, 11 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Apr 24, 2015
First posted: Apr 30, 2015
Start: Apr 2015
Primary completionActual: Sep 2015
CompletionActual: Nov 2015
Results first posted: Aug 31, 2016
Last update: Aug 31, 2016

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Aug 31, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02430870
Lead sponsor: Takeda
Responsible party: Sponsor
First posted: Apr 30, 2015
Start date: Apr 2015
Primary completion: Sep 2015
Completion: Nov 2015
Results posted: Aug 31, 2016
Last update: Aug 31, 2016

Study contacts

Medical Director

study director · Takeda

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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