Hypogonadotropic Hypogonadism
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to evaluate the effects on serum testosterone after 4 weeks of subcutaneous (SC) dose administration, with different doses and dosing frequencies of TAK-448 to overweight/obese males with hypogonadotropic hypogonadism.
Detailed description
The drug being tested in this study is called TAK-448. TAK-448 is being tested to treat overweight/obese males with hypogonadotropic hypogonadism. This study will look at the effects of TAK-448 on serum testosterone at different doses and different dosing frequencies. The study will enroll 15 patients. There will be 5 cohorts and participants will be assigned to cohorts in sequential order. Cohorts will be assigned to the following treatment groups: * TAK-448 3 µg once weekly * TAK-448 1 µg once weekly * TAK-448 0.3 µg once weekly * TAK-448 0.3 µg twice weekly * TAK-448 0.1 µg twice weekly All participants will be administered study drug via SC injection once or twice a week depending on their assigned cohort for four weeks. This single-center trial will be conducted in the United Kingdom. The overall time to participate in this study is up to 32 days. Participants will make multiple visits to the clinic (depending once-weekly or twice-weekly dosing), and will be contacted by telephone 1 week after last dose of study drug for a follow-up assessment.
Interventions
DRUGTAK-448
TAK-448 solution for subcutaneous injection
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. The participant has two morning total serum testosterone (ST) concentrations ≤12.0 nmol/L (≤3.46 ng/mL) taken during the Screening period. 4. Is male and aged 18 to 60 years, inclusive. 5. Has a body mass index (BMI) between 25.0 and 50.0 kg/m\^2, inclusive. 6. If diagnosed with type II diabetes mellitus (T2DM), has a glycosylated hemoglobin (HbA1c) concentration \<12% at Screening and is on a stable dose of up to 4 diabetes therapies (including insulin and/or glucagon-like peptide-1 therapies). 7. Has a luteinizing hormone (LH) concentration \<8 IU/L at Screening. 8. 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.
Exclusion criteria
1. Has received any investigational compound within 30 days prior to Screening. 2. Has received TAK-448 in a previous clinical study, or previous cohort. 3. Is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. 4. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality (other than T2DM, its complications and associated conditions), which may impact the ability of the participant to participate or potentially confound the study results. 5. Has a recent history or clinical manifestations of significant cardiovascular disease (CVD) - such as a history of myocardial infarction or stroke in the 6 months preceding the Screening visit or has untreated peripheral arterial disease. 6. Has a history of hypersensitivity or allergies to any component of the formulation of TAK-448. 7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to Screening. 8. Is required to take excluded medications, supplements, or food products. 9. Intends to donate sperm during the course of this study or for 12 weeks after the last dose of study drug. 10. Has clinical evidence of anatomic or pathological hypothalamic/pituitary disease. 11. 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-448, or a similar drug in the same class that might interfere with the conduct of the study. 12. Has a history of cancer (including prostate cancer), with the exception of basal cell carcinoma which has been in remission for at least 5 years prior to Screening. 13. Has a history of or present prostate disease (including benign prostatic hyperplasia) or prostate-specific antigen (PSA) is \>4 ng/mL at Screening. 14. Has a known history of human immunodeficiency virus infection at Screening. 15. Is deemed by the study team to have poor peripheral venous access. 16. Has donated or lost 450 mL or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days prior to Screening, or is planning to donate blood for 12 weeks after the last dose of study medication. 17. Has a Screening or Day -1 abnormal (clinically significant) electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature of the principal investigator or medically qualified subinvestigator. 18. Has abnormal Screening or Day -1 laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>2× the upper limits of normal (ULN). 19. The participant, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason. 20. Has had more than two severe hypoglycemic events (requiring third party assistance) within 6 months prior to the Screening Visit. 21. Has a diagnosis of type 1 diabetes mellitus. 22. Has a history of diabetic ketoacidosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Serum Concentration (Ctrough) of Free Serum Testosterone for Twice Weekly Dosing Groups | Day 25 pre-dose | Trough serum concentration of free ST, defined as lowest baseline concentration compared to pre-dose of the last dose. |
| Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Free Serum Testosterone for Twice Weekly Dosing Groups | Baseline and Day 25 pre-dose and multiple time points (up to 72 hours) post dose | Area under the PD free ST concentration-time curve from the time 0 to 72 hours, calculated using the linear trapezoidal rule for baseline profile and those obtained after first and last dose. |
| Trough Serum Concentration (Ctrough) of Total Serum Testosterone for Once Weekly Dosing Groups | Day 22 pre-dose | Trough serum concentration of total ST, defined as lowest baseline concentration compared to pre-dose of the last dose. |
| Trough Serum Concentration (Ctrough) of Total Serum Testosterone for Twice Weekly Dosing Group | Day 25 pre-dose | Trough serum concentration of total ST, defined as lowest baseline concentration compared to pre-dose of the last dose. |
| Trough Serum Concentration (Ctrough) of Free Serum Testosterone for Once Weekly Dosing Groups | Day 22 pre-dose | Trough serum concentration of free ST, defined as lowest baseline concentration compared to pre-dose of the last dose. |
| Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Total Serum Testosterone for Once Weekly Dosing Groups | Baseline and Day 22 pre-dose and multiple time points (up to 72 hours) post dose | Area under the pharmacodynamic (PD) total serum testosterone (ST) concentration-time curve from the time 0 to 72 hours, calculated using the linear trapezoidal rule for baseline profile and those obtained after first and last dose. |
| Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Total Serum Testosterone for Twice Weekly Dosing Groups | Baseline and Day 25 pre-dose and multiple time points (up to 72 hours) post dose | Area under the PD total ST concentration-time curve from the time 0 to 72 hours, calculated using the linear trapezoidal rule for baseline profile and those obtained after first and last dose. |
| Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Free Serum Testosterone for Once Weekly Dosing Groups | Baseline and Day 22 pre-dose and multiple time points (up to 72 hours) post dose | Area under the PD free ST concentration-time curve from the time 0 to 72 hours, calculated using the linear trapezoidal rule for baseline profile and those obtained after first and last dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-∞): Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-448F | Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose | AUC(0-∞) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. |
| AUC(0-tlqc): Mean Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-448F | Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose | AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]). |
| Mean Terminal Phase Elimination Half-life (T1/2) for TAK-448F | Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose | Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. |
| Cmax: Mean Maximum Observed Plasma Concentration for TAK-448 Free Base Form (TAK-448F) | Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United Kingdom from 10 February 2015 to 3 November 2015.
Pre-assignment details
Overweight/obese male participants with a diagnosis of hypogonadotropic hypogonadism were enrolled in 1 of 5 treatment groups: once weekly TAK-448 3 µg, 1 µg or 0.3 µg or twice weekly TAK-448 0.3 µg or 0.1 µg.
Participants by arm
| Arm | Count |
|---|---|
| TAK-448 3 µg Once Weekly TAK-448 3 µg, subcutaneous injection, once weekly on Days 1, 8, 15 and 22. | 3 |
| TAK-448 1 µg Once Weekly TAK-448 1 µg, subcutaneous injection, once weekly on Days 1, 8, 15 and 22. | 3 |
| TAK-448 0.3 µg Once Weekly TAK-448 0.3 µg, subcutaneous injection, once weekly on Days 1, 8, 15 and 22. | 3 |
| TAK-448 0.3 µg Twice Weekly TAK-448 0.3 µg, subcutaneous injection, twice weekly on Days 1, 4, 8, 11, 15, 18, 22, and 25. | 3 |
| TAK-448 0.1 µg Twice Weekly TAK-448 0.1 µg, subcutaneous injection, twice weekly on Days 1, 4, 8, 11, 15, 18, 22, and 25. | 3 |
| Total | 15 |
Baseline characteristics
| Characteristic | TAK-448 1 µg Once Weekly | Total | TAK-448 0.1 µg Twice Weekly | TAK-448 3 µg Once Weekly | TAK-448 0.3 µg Twice Weekly | TAK-448 0.3 µg Once Weekly |
|---|---|---|---|---|---|---|
| Age, Continuous | 50.7 years STANDARD_DEVIATION 4.62 | 50.8 years STANDARD_DEVIATION 9.04 | 45.0 years STANDARD_DEVIATION 19.16 | 50.7 years STANDARD_DEVIATION 8.02 | 56.0 years STANDARD_DEVIATION 3.61 | 51.7 years STANDARD_DEVIATION 3.79 |
| Alcohol Classification Has never drunk | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Alcohol Classification Is an ex-drinker | 1 participants | 4 participants | 1 participants | 0 participants | 1 participants | 1 participants |
| Alcohol Classification Is current drinker | 2 participants | 10 participants | 2 participants | 3 participants | 2 participants | 1 participants |
| Body Mass Index | 37 kg/m^2 STANDARD_DEVIATION 1 | 36 kg/m^2 STANDARD_DEVIATION 4 | 34 kg/m^2 STANDARD_DEVIATION 4 | 36 kg/m^2 STANDARD_DEVIATION 8 | 36 kg/m^2 STANDARD_DEVIATION 2 | 36 kg/m^2 STANDARD_DEVIATION 2 |
| Caffeine Consumption No | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Caffeine Consumption Yes | 3 participants | 14 participants | 3 participants | 3 participants | 2 participants | 3 participants |
| Height | 174 cm STANDARD_DEVIATION 6 | 176 cm STANDARD_DEVIATION 10 | 178 cm STANDARD_DEVIATION 12 | 168 cm STANDARD_DEVIATION 7 | 178 cm STANDARD_DEVIATION 6 | 181 cm STANDARD_DEVIATION 18 |
| Race/Ethnicity, Customized Asian | 0 participants | 2 participants | 0 participants | 2 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 3 participants | 13 participants | 3 participants | 1 participants | 3 participants | 3 participants |
| Region of Enrollment United Kingdom | 3 participants | 15 participants | 3 participants | 3 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 15 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants |
| Smoking Classification Has never smoked | 0 participants | 5 participants | 1 participants | 3 participants | 1 participants | 0 participants |
| Smoking Classification Is an ex-smoker | 3 participants | 9 participants | 2 participants | 0 participants | 2 participants | 2 participants |
| Smoking Classification Is current smoker | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Weight | 113 kg STANDARD_DEVIATION 10 | 112 kg STANDARD_DEVIATION 19 | 110 kg STANDARD_DEVIATION 26 | 104 kg STANDARD_DEVIATION 30 | 115 kg STANDARD_DEVIATION 7 | 119 kg STANDARD_DEVIATION 26 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 3 | 1 / 3 | 1 / 3 | 3 / 3 | 1 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Free Serum Testosterone for Once Weekly Dosing Groups
Area under the PD free ST concentration-time curve from the time 0 to 72 hours, calculated using the linear trapezoidal rule for baseline profile and those obtained after first and last dose.
Time frame: Baseline and Day 22 pre-dose and multiple time points (up to 72 hours) post dose
Population: PD set included all participants who received at least one dose of study drug and had at least 1 valid PD measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-448 3 µg Once Weekly | Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Free Serum Testosterone for Once Weekly Dosing Groups | 3.55 percent change | Standard Deviation 9.08 |
| TAK-448 1 µg Once Weekly | Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Free Serum Testosterone for Once Weekly Dosing Groups | 11.1 percent change | Standard Deviation 28 |
| TAK-448 0.3 µg Once Weekly | Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Free Serum Testosterone for Once Weekly Dosing Groups | 7.92 percent change | Standard Deviation 8.88 |
Primary
Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Free Serum Testosterone for Twice Weekly Dosing Groups
Area under the PD free ST concentration-time curve from the time 0 to 72 hours, calculated using the linear trapezoidal rule for baseline profile and those obtained after first and last dose.
Time frame: Baseline and Day 25 pre-dose and multiple time points (up to 72 hours) post dose
Population: PD set included all participants who received at least one dose of study drug and had at least 1 valid PD measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-448 3 µg Once Weekly | Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Free Serum Testosterone for Twice Weekly Dosing Groups | -9.00 percent change | Standard Deviation 4.23 |
| TAK-448 1 µg Once Weekly | Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Free Serum Testosterone for Twice Weekly Dosing Groups | 20.5 percent change | Standard Deviation 5.33 |
Primary
Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Total Serum Testosterone for Once Weekly Dosing Groups
Area under the pharmacodynamic (PD) total serum testosterone (ST) concentration-time curve from the time 0 to 72 hours, calculated using the linear trapezoidal rule for baseline profile and those obtained after first and last dose.
Time frame: Baseline and Day 22 pre-dose and multiple time points (up to 72 hours) post dose
Population: PD set included all participants who received at least one dose of study drug and had at least 1 valid PD measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-448 3 µg Once Weekly | Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Total Serum Testosterone for Once Weekly Dosing Groups | 1.9 percent change | Standard Deviation 11.3 |
| TAK-448 1 µg Once Weekly | Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Total Serum Testosterone for Once Weekly Dosing Groups | 13.5 percent change | Standard Deviation 24.9 |
| TAK-448 0.3 µg Once Weekly | Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Total Serum Testosterone for Once Weekly Dosing Groups | 14.9 percent change | Standard Deviation 16.3 |
Primary
Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Total Serum Testosterone for Twice Weekly Dosing Groups
Area under the PD total ST concentration-time curve from the time 0 to 72 hours, calculated using the linear trapezoidal rule for baseline profile and those obtained after first and last dose.
Time frame: Baseline and Day 25 pre-dose and multiple time points (up to 72 hours) post dose
Population: PD set included all participants who received at least one dose of study drug and had at least 1 valid PD measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-448 3 µg Once Weekly | Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Total Serum Testosterone for Twice Weekly Dosing Groups | -2.8 percent change | Standard Deviation 3.7 |
| TAK-448 1 µg Once Weekly | Percent Change From Baseline in Mean Area Under the Effect Curve From Time 0 to 72 Hours (AUEC72) of Total Serum Testosterone for Twice Weekly Dosing Groups | 6.0 percent change | Standard Deviation 12.3 |
Primary
Trough Serum Concentration (Ctrough) of Free Serum Testosterone for Once Weekly Dosing Groups
Trough serum concentration of free ST, defined as lowest baseline concentration compared to pre-dose of the last dose.
Time frame: Day 22 pre-dose
Population: PD set included all participants who received at least one dose of study drug and had at least 1 valid PD measure. Number of participants analyzed is number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-448 3 µg Once Weekly | Trough Serum Concentration (Ctrough) of Free Serum Testosterone for Once Weekly Dosing Groups | 0.16 nmol/L | Standard Deviation 0.03 |
| TAK-448 1 µg Once Weekly | Trough Serum Concentration (Ctrough) of Free Serum Testosterone for Once Weekly Dosing Groups | 0.12 nmol/L | Standard Deviation 0.07 |
| TAK-448 0.3 µg Once Weekly | Trough Serum Concentration (Ctrough) of Free Serum Testosterone for Once Weekly Dosing Groups | 0.21 nmol/L | Standard Deviation 0.004 |
Primary
Trough Serum Concentration (Ctrough) of Free Serum Testosterone for Twice Weekly Dosing Groups
Trough serum concentration of free ST, defined as lowest baseline concentration compared to pre-dose of the last dose.
Time frame: Day 25 pre-dose
Population: PD set included all participants who received at least one dose of study drug and had at least 1 valid PD measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-448 3 µg Once Weekly | Trough Serum Concentration (Ctrough) of Free Serum Testosterone for Twice Weekly Dosing Groups | 0.12 nmol/L | Standard Deviation 0.09 |
| TAK-448 1 µg Once Weekly | Trough Serum Concentration (Ctrough) of Free Serum Testosterone for Twice Weekly Dosing Groups | 0.20 nmol/L | Standard Deviation 0.06 |
Primary
Trough Serum Concentration (Ctrough) of Total Serum Testosterone for Once Weekly Dosing Groups
Trough serum concentration of total ST, defined as lowest baseline concentration compared to pre-dose of the last dose.
Time frame: Day 22 pre-dose
Population: PD set included all participants who received at least one dose of study drug and had at least 1 valid PD measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-448 3 µg Once Weekly | Trough Serum Concentration (Ctrough) of Total Serum Testosterone for Once Weekly Dosing Groups | 5.4 nmol/L | Standard Deviation 1.3 |
| TAK-448 1 µg Once Weekly | Trough Serum Concentration (Ctrough) of Total Serum Testosterone for Once Weekly Dosing Groups | 4.4 nmol/L | Standard Deviation 3.1 |
| TAK-448 0.3 µg Once Weekly | Trough Serum Concentration (Ctrough) of Total Serum Testosterone for Once Weekly Dosing Groups | 8.7 nmol/L | Standard Deviation 1.3 |
Primary
Trough Serum Concentration (Ctrough) of Total Serum Testosterone for Twice Weekly Dosing Group
Trough serum concentration of total ST, defined as lowest baseline concentration compared to pre-dose of the last dose.
Time frame: Day 25 pre-dose
Population: PD set included all participants who received at least one dose of study drug and had at least 1 valid PD measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-448 3 µg Once Weekly | Trough Serum Concentration (Ctrough) of Total Serum Testosterone for Twice Weekly Dosing Group | 4.7 nmol/L | Standard Deviation 2.8 |
| TAK-448 1 µg Once Weekly | Trough Serum Concentration (Ctrough) of Total Serum Testosterone for Twice Weekly Dosing Group | 6.9 nmol/L | Standard Deviation 2.1 |
Secondary
AUC(0-∞): Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-448F
AUC(0-∞) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.
Time frame: Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose
Population: PK set included all participants who received at least one dose of study drug and had at least 1 measurable concentration of TAK-448F. Here, 'n' is the participants who were analyzed at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-448 3 µg Once Weekly | AUC(0-∞): Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-448F | Day 22 (n=3, 1, 1) | 122.33 pg*hr/mL | Standard Deviation 10.477 |
| TAK-448 3 µg Once Weekly | AUC(0-∞): Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-448F | Day 1 (n=3, 0 1) | 112.00 pg*hr/mL | Standard Deviation 5.686 |
| TAK-448 1 µg Once Weekly | AUC(0-∞): Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-448F | Day 22 (n=3, 1, 1) | 33.30 pg*hr/mL | — |
| TAK-448 1 µg Once Weekly | AUC(0-∞): Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-448F | Day 1 (n=3, 0 1) | NA pg*hr/mL | — |
| TAK-448 0.3 µg Once Weekly | AUC(0-∞): Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-448F | Day 1 (n=3, 0 1) | NA pg*hr/mL | — |
| TAK-448 0.3 µg Once Weekly | AUC(0-∞): Mean Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-448F | Day 22 (n=3, 1, 1) | NA pg*hr/mL | — |
Secondary
AUC(0-tlqc): Mean Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-448F
AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]).
Time frame: Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose
Population: PK set included all participants who received at least one dose of study drug and had at least 1 measurable concentration of TAK-448F.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-448 3 µg Once Weekly | AUC(0-tlqc): Mean Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-448F | Day 22 | 95.20 pg*hr/mL | Standard Deviation 11.914 |
| TAK-448 3 µg Once Weekly | AUC(0-tlqc): Mean Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-448F | Day 1 | 92.23 pg*hr/mL | Standard Deviation 6.732 |
| TAK-448 1 µg Once Weekly | AUC(0-tlqc): Mean Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-448F | Day 22 | 18.37 pg*hr/mL | Standard Deviation 3.069 |
| TAK-448 1 µg Once Weekly | AUC(0-tlqc): Mean Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-448F | Day 1 | 19.00 pg*hr/mL | Standard Deviation 3.47 |
| TAK-448 0.3 µg Once Weekly | AUC(0-tlqc): Mean Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-448F | Day 22 | NA pg*hr/mL | — |
| TAK-448 0.3 µg Once Weekly | AUC(0-tlqc): Mean Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-448F | Day 1 | NA pg*hr/mL | — |
Secondary
Cmax: Mean Maximum Observed Plasma Concentration for TAK-448 Free Base Form (TAK-448F)
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose
Population: Pharmacokinetic (PK) set included all participants who received at least one dose of study drug and had at least 1 measurable concentration of TAK-448F.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-448 3 µg Once Weekly | Cmax: Mean Maximum Observed Plasma Concentration for TAK-448 Free Base Form (TAK-448F) | Day 1 | 39.50 pg/mL | Standard Deviation 4.943 |
| TAK-448 3 µg Once Weekly | Cmax: Mean Maximum Observed Plasma Concentration for TAK-448 Free Base Form (TAK-448F) | Day 22 | 40.10 pg/mL | Standard Deviation 6.344 |
| TAK-448 1 µg Once Weekly | Cmax: Mean Maximum Observed Plasma Concentration for TAK-448 Free Base Form (TAK-448F) | Day 1 | 10.46 pg/mL | Standard Deviation 1.484 |
| TAK-448 1 µg Once Weekly | Cmax: Mean Maximum Observed Plasma Concentration for TAK-448 Free Base Form (TAK-448F) | Day 22 | 12.27 pg/mL | Standard Deviation 3.618 |
| TAK-448 0.3 µg Once Weekly | Cmax: Mean Maximum Observed Plasma Concentration for TAK-448 Free Base Form (TAK-448F) | Day 1 | NA pg/mL | — |
| TAK-448 0.3 µg Once Weekly | Cmax: Mean Maximum Observed Plasma Concentration for TAK-448 Free Base Form (TAK-448F) | Day 22 | NA pg/mL | — |
Secondary
Mean Terminal Phase Elimination Half-life (T1/2) for TAK-448F
Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Time frame: Day 1 and Day 22 pre-dose and at multiple time points (up to 8 hours) post-dose
Population: Pharmacokinetic (PK) set included all participants who received at least one dose of study drug and had at least 1 measurable concentration of TAK-448F. Here, 'n' is the participants who were analyzed at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-448 3 µg Once Weekly | Mean Terminal Phase Elimination Half-life (T1/2) for TAK-448F | Day 1 (n=3, 0, 1) | 1.800 hr | Standard Deviation 0.0751 |
| TAK-448 3 µg Once Weekly | Mean Terminal Phase Elimination Half-life (T1/2) for TAK-448F | Day 22 (n=3, 1, 1) | 2.073 hr | Standard Deviation 0.192 |
| TAK-448 1 µg Once Weekly | Mean Terminal Phase Elimination Half-life (T1/2) for TAK-448F | Day 22 (n=3, 1, 1) | 1.150 hr | — |
| TAK-448 1 µg Once Weekly | Mean Terminal Phase Elimination Half-life (T1/2) for TAK-448F | Day 1 (n=3, 0, 1) | NA hr | — |
| TAK-448 0.3 µg Once Weekly | Mean Terminal Phase Elimination Half-life (T1/2) for TAK-448F | Day 1 (n=3, 0, 1) | NA hr | — |
| TAK-448 0.3 µg Once Weekly | Mean Terminal Phase Elimination Half-life (T1/2) for TAK-448F | Day 22 (n=3, 1, 1) | NA hr | — |