Phase 1
Completed N=13
An [^11C]T-773 Positron Emission Tomography (PET) Study to Determine Phosphodiesterase10A Occupancy by TAK-063
Healthy Volunteers
Source: ClinicalTrials.gov NCT02370602 ↗
Enrolled (actual)
13
Serious AEs
0.0%
Results posted
Mar 2015
Primary outcomePrimary: Phosphodiesterase 10A (PDE10A) Occupancy of Brain Regions With [^11C]T-773 at 3 Hours Following a Single Dose of TAK-063 — 14.400; 26.650; 39.333; 53.633 Percent
Summary
The purpose of this study is to estimate phosphodiesterase 10A (PDE10A) occupancy in brain following a single dose of TAK-063.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phosphodiesterase 10A (PDE10A) Occupancy of Brain Regions With [^11C]T-773 at 3 Hours Following a Single Dose of TAK-063 |
14.400; 26.650; 39.333; 53.633; 69.350 | — |
| SECONDARY Phosphodiesterase 10A (PDE10A) Occupancy of Brain Regions With [^11C]T-773 at 23 Hours Following a Single Dose of TAK-063 |
-2.250; 14.750; 18.800; 24.167 | — |
| SECONDARY Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event |
38.5; 75.0 | — |
| SECONDARY Percentage of Participants With Markedly Abnormal Safety Laboratory Findings |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Markedly Abnormal Vital Sign Measurements |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters |
7.7; 50.0; 50.0; 33.3; 66.7; 0 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for TAK-063 and TAK-063 Metabolite M-I |
11.25; 22.78; 80.67; 77.05; 258.75; 15.60 | — |
| SECONDARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-063 and TAK-063 Metabolite M-I |
1.25; 2.99; 1.33; 2.33; 2.25; 1.50 | — |
| SECONDARY AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-063 and TAK-063 Metabolite M-I |
91.42; 318.56; 774.76; 897.17; 3288.62; 88.74 | — |
| SECONDARY AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-063 and TAK-063 Metabolite M-I |
92.55; 324.98; 774.44; 910.12; 3289.62; 89.64 | — |
| SECONDARY Average Plasma Concentration on Day 1 (Cavg) for TAK-063 and TAK-063 Metabolite M-I |
3.86; 13.54; 32.27; 37.92; 137.07; 3.74 | — |
| SECONDARY CL/F: Oral Clearance of TAK-063 |
26.19; 18.31; 24.90; 88.86; 252.33 | — |
| SECONDARY Ratio of TAK-063 Metabolite Cmax to TAK-063 Cmax |
1.30; 0.83; 0.65; 0.99; 0.55 | — |
| SECONDARY Ratio of TAK-063 Metabolite M-I AUC( 0-24) to TAK-063 AUC (0-24) |
0.93; 0.75; 0.66; 0.89; 0.54 | — |
| SECONDARY AUC During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 3 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I |
9.51; 25.68; 63.18; 82.25; 269.32; 10.23 | — |
| SECONDARY Cavg During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 3 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I |
7.61; 20.54; 50.54; 65.80; 215.46; 8.18 | — |
| SECONDARY AUC During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 23 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I |
1.75; 11.44; 21.22; 21.15; 1.43; 8.20 | — |
| SECONDARY Cavg During the Positron Emission Tomography (PET) Scan Period (AUC(Scan)) at 23 Hours Post-dose for TAK-063 and TAK-063 Metabolite M-I |
1.40; 9.15; 16.97; 16.92; 1.15; 6.56 | — |
Eligibility Criteria
Inclusion Criteria
- Has never previously participated in a positron emission tomography (PET) study (lifetime).
- In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
- The participant, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
- Is a healthy adult male, as determined by a physician based upon medical history and physical examination findings at Screening.
- Is aged 20 to 45 years, inclusive, at the time of informed consent.
- Weighs at least 50 kg and less than 100 kg and has a body mass index (BMI) between 18 and 32 kg/m^2 inclusive at Screening.
- A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.
- Has clinical laboratory evaluations (including clinical chemistry, hematology and complete urinalysis) within the reference range for the testing laboratory, unless the results are deemed not to be clinically significant (CS) by the investigator or sponsor at screening. Participants must have normal hemoglobin levels.
- Has a normal magnetic resonance imaging (MRI) scan or findings that are deemed not clinically significant at screening (the MRI scan may be performed on a day after other screening activities have been performed but before dosing).
Exclusion Criteria
- Has received any investigational compound within 90 days prior to Screening.
- Has received TAK-063 in a previous clinical study or as a therapeutic agent.
- Is an immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
- Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
- Has a known hypersensitivity to any component of the formulation of TAK-063 or [^11C]T-773.
- Has a positive urine drug result for drugs of abuse or a positive breathalyzer test for alcohol at Screening or Day -1.
- 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 until discharge from the Phase 1 unit and drugs throughout the study.
- Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products table.
- Intends to donate sperm during the course of the study or within 12 weeks after last dose.
- Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-063 or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.
- The participant, in the opinion of the investigator, has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent [more than once per week] occurrence of heartburn, or any surgical intervention [eg, cholecystectomy]).
- Has a history of cancer, except basal cell c
Data sourced from ClinicalTrials.gov (NCT02370602). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.