Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TAK-385 · 7 trials · 6 indications
Castration rate is defined as the observed percentage of participants who have testosterone concentrations less than (\<) 50 nanogram per deciliter (ng/dL) (1.73 nanomole per liter \[nmol/L\]) at all scheduled visits.
Measured by Dual-energy X-ray absorptiometry (DXA)
Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through the last visit (Week 16)
Vital signs will include body temperature, sitting blood pressure and pulse (bpm).
NTx is one of the biochemical bone metabolism markers
BAP is one of the biochemical bone metabolism markers
Blood loss will be assessed using the Pictorial Blood Loss Assessment Chart (PBAC).
Pelvic pain will be assessed using the VAS as pain evaluation scale.
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Radioactivity corresponds to no more than (NMT) 4.7 millibecquerel (MBq) (127 microcurie \[mCi\]). Cmax was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by accelerator mass spectrometry (AMS) method.
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385).
Maximum observed concentration (Cmax) is the peak concentration of a drug after administration, obtained directly from the concentration-time curve. Radioactivity corresponds to NMT 4.7 MBq (127 mCi). Cmax was measured in nanogram equivalent per milliliter (ng eq/mL) and was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method.
Maximum observed concentration (Cmax) is the peak concentration of a drug after administration, obtained directly from the concentration-time curve. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385).
AUC(0-inf) is measure of area under the curve from time 0 to infinity. Radioactivity corresponds to NMT 4.7 MBq (127 mCi). AUC(0-inf) was measured in nanogram equivalent\*hour per milliliter (ng eq\*hr/mL) and was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method.
AUC(0-inf) is area under the concentration-time curve from time 0 to infinity. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385) .
AUC(0-168) is measure of area under the curve over the dosing interval (tau),where tau is the length of the dosing interval: 168 hours in this study (AUC(0-168\]). Radioactivity corresponds to NMT 4.7 MBq (127 mCi). It was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method.
AUC(0-168) is measure of area under the curve over the dosing interval (tau) (AUC(0-tau\]), where tau is the length of the dosing interval -168 hours in this study). Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385).
Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood. Radioactivity corresponds to NMT 4.7 MBq (127 mCi). It was calculated as disintegration per minute per mL (DPM/mL). Total \[14C\]-TAK-385 determination of plasma and whole blood samples was determined by AMS method.
Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood. Plasma concentrations of TAK-385 were measured by high-performance liquid chromatography with tandem mass spectrometry method (LC-MS/MS). Correction of the LC-MS/MS derived concentrations were based upon the specific activity of the administered radiolabelled drug product (\[14C\]-TAK-385).
Overall cumulative percent of radioactive dose recovered in urine and feces is the total radioactivity excreted in urine and feces divided by the amount of total radioactivity dosed for each participant. Total \[14-C\] determination of urine and feces samples were determined by Liquid Scintillation Counting (LSC).
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. Radioactivity corresponds to NMT 37.0 kilobecquerel (kBq) (1000 nanocurie \[nCi\]). Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS.
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS.
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
AUC(0-inf) is measure of area under the curve from time 0 to Infinity. Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).AUC(0-inf) was corrected according to Hamilton Pool result.Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS.
AUC(0-inf) is measure of area under the curve from time 0 to Infinity.
AUC(0-168) is measure of area under the curve over the dosing interval (tau), where tau is the length of the dosing interval :168 hours in this study (AUC(0-tau\]). AUC(0-168) was corrected according to Hamilton Pool result.Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS.
AUC(0-168) is measure of area under the curve over the dosing interval (tau),where tau is the length of the dosing interval: 168 hours in this study (AUC(0-tau\]). AUC was corrected using the Hamilton Pool Data to get an AUC for TAK-385.
Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood. Radioactivity corresponds to NMT 37.0 kBq (1000 nCi).Total radioactivity and \[14C\]-TAK-385 determination of plasma samples was determined by AMS.
Terminal phase elimination half-life (t1/2z) is the time required for half of the drug to be eliminated from the blood.
Absolute bioavailability, defined as the fraction or percentage of the unchanged, orally administered dose that is systemically available, relative to the total dose administered intravenously. AUC was corrected using the Hamilton Pool Data to get an AUC for TAK-385
Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from feces, calculated as percentage of recovered radioactivity, are reported. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total radioactivity (total \[14\]C).Radioactivity corresponds to NMT 4.7 MBq (127 mCi).
Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from urine, calculated as percentage of recovered radioactivity, are reported. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total radioactivity (total \[14\]C).Radioactivity corresponds to NMT 4.7 MBq (127 mCi).
Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from feces, calculated as percentage of dose. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total \[14\]C.
Amount of total \[14\]C, TAK-385, metabolite A, B, and C, and others excreted from urine, calculated as percentage of dose. Others were calculated by subtraction of the sum of the values for TAK-385, Metabolite-A, Metabolite-B, and Metabolite-C from the value of the total \[14\]C.
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
Percentage of \[14\]C as measured from TAK-385, metabolite A and B, and metabolite C in the plasma pools were calculated as the percentage of dose administered.
DLTs were defined as treatment-related adverse events (AEs) that occurred within the first 28 days of treatment as per common terminology criteria for adverse events (CTCAE) version 4.03: any grade 3 or higher toxicity; QT/Fridericia corrected QT (QTcF) greater than (\>) 500 millisecond (msec) after treatment initiation; QT/QTcF interval prolongation \>60 msec postdose.
Laboratory test abnormalities were graded using the CTCAE. The grades were: Grade 2- (moderate) minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activity of daily living (ADL); Grade 3- (severe) medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limited self-care ADL. Data has been presented for any Grade 2 or higher event in the laboratory test abnormalities.
Laboratory test abnormalities were graded using the CTCAE. The grades were: Grade 2- (moderate) minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL; Grade 3- (severe) medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limited self-care ADL. Data has been presented for any Grade 2 or higher event in the laboratory test abnormalities. Here aspartate aminotransferase (AST) (glutamic-oxaloacetic transaminase \[GOT\]) High, creatine kinase (CK) (creatine phosphokinase \[CPK\]) High, prothrombin time (PT)-international normalized ratio (INR) High.
Here "BP" is blood pressure.
| Arm | Type | Description |
|---|---|---|
| TAK-385 | EXPERIMENTAL | TAK-385 320 mg, tablets, orally, once, on Day 1, followed by TAK-385 120 mg, orally, once daily for 24 weeks. Each participant may have one upward dose adjustment of 40 mg for efficacy and/or one downward dose adjustment of 40 mg for safety during the study. |
| Degarelix | ACTIVE_COMPARATOR | Degarelix 240 mg, injection, subcutaneous, on Day 1, followed by degarelix 80 mg, injection, subcutaneous, once every four weeks, for 24 weeks. |
| Placebo | PLACEBO_COMPARATOR | - |
| TAK-385 10 mg QD | EXPERIMENTAL | - |
| TAK-385 20 mg QD | EXPERIMENTAL | - |
| TAK-385 40 mg QD | EXPERIMENTAL | - |
| Leuplin | OTHER | - |
| TAK-385 40 mg (Group A) | EXPERIMENTAL | A single oral dose of TAK-385 40 milligram (mg) (one tablet) in fasted condition without breakfast in Period 1, followed by a minimum 14-day washout period between study drugs, further followed by a single oral dose of TAK-385 40 mg (one tablet) before breakfast in Period 2, followed by a minimum 14-day washout period between study drugs and further followed by a single oral dose of TAK-385 40 mg (one tablet) after breakfast in Period 3. |
| TAK-385 40 mg (Group B) | EXPERIMENTAL | A single oral dose of TAK-385 40 mg (one tablet) before breakfast in Period 1, followed by a minimum 14-day washout period between study drugs, further followed by a single oral dose of TAK-385 40 mg (one tablet) after breakfast in Period 2, followed by a minimum 14-day washout period between study drugs and, further followed by a single oral dose of TAK-385 40 mg (one tablet) in fasted condition without breakfast in Period 3. |
| TAK-385 40 mg (Group C) | EXPERIMENTAL | A single oral dose of TAK-385 40 mg (one tablet) after breakfast in Period 1, followed by a minimum 14-day washout period between study drugs, further followed by a single oral dose of TAK-385 40 mg (one tablet) in fasted condition without breakfast in Period 2, followed by a minimum 14-day washout period between study drugs and, further followed by a single oral dose of TAK-385 40 mg (one tablet) before breakfast in Period 3. |
| TAK-385 40 mg (Group D) | EXPERIMENTAL | A single oral dose of TAK-385 40 mg (one tablet) in fasted condition without breakfast in Period 1, followed by a minimum 14-day washout period between study drugs, further followed by a single oral dose of TAK-385 40 mg (one tablet) after breakfast in Period 2, followed by a minimum 14-day washout period between study drugs and, further followed by a single oral dose of TAK-385 40 mg (one tablet) before breakfast in Period 3. |
| TAK-385 40 mg (Group E) | EXPERIMENTAL | A single oral dose of TAK-385 40 mg (one tablet) before breakfast in Period 1, followed by a minimum 14-day washout period between study drugs, further followed by a single oral dose of TAK-385 40 mg (one tablet) in fasted condition without breakfast in Period 2, followed by a minimum 14-day washout period between study drugs and, further followed by a single oral dose of TAK-385 40 mg (one tablet) after breakfast in Period 3. |
| TAK-385 40 mg (Group F) | EXPERIMENTAL | A single oral dose of TAK-385 40 mg (one tablet) after breakfast in Period 1, followed by a minimum 14-day washout period between study drugs, further followed by a single oral dose of TAK-385 40 mg (one tablet) before breakfast in Period 2, followed by a minimum 14-day washout period between study drugs and, further followed by a single oral dose of TAK-385 40 mg (one tablet) in fasted condition without breakfast in Period 3. |
| Part 1: [14C]-TAK-385 | EXPERIMENTAL | \[14C\]-TAK-385 80 mg, solution, orally, once on Day 1. |
| Part 2: TAK-385 + [14C]-TAK-385 IV | EXPERIMENTAL | TAK-385 80 mg, tablets, orally, and \[14C\]-TAK-385 80 μg, infusion, intravenous once on Day 1. |
| Part A Cohort 1: TAK-385 320 mg + TAK-385 80 mg | EXPERIMENTAL | TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 80 mg maintenance dose, tablet, orally, once daily through Days 2 to 28. |
| Part A Cohort 2: TAK-385 320 mg + TAK-385 120 mg | EXPERIMENTAL | TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 120 mg maintenance dose, tablet, orally, once daily through Days 2 to 28. |
| Part A Cohort 3: TAK-385 320 mg + TAK-385 160 mg | EXPERIMENTAL | TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 160 mg maintenance dose, tablet, orally, once daily through Days 2 to 28. |
| Part A Cohort 4: TAK-385 360 mg + TAK-385 120 mg | EXPERIMENTAL | TAK-385 360 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 120 mg maintenance dose, tablet, orally, once daily through Days 2 to 28. |
| Part B Cohort 1: TAK-385 320 mg + TAK-385 80 mg | EXPERIMENTAL | TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 80 mg maintenance dose, tablet, orally, once daily through Days 2 to 672. |
| Part B Cohort 2: TAK-385 320 mg + TAK-385 120 mg | EXPERIMENTAL | TAK-385 320 mg loading dose, tablet, orally, once on Day 1, followed by TAK-385 120 mg maintenance dose, tablet, orally, once daily through Days 2 to 672. |
| Name | Type | Description |
|---|---|---|
| TAK-385 | DRUG | TAK-385 tablet |
| Degarelix | DRUG | Degarelix injection |
| Placebo | DRUG | TAK-385 placebo-matching tablets, orally, once daily and leuprorelin acetate placebo injection, subcutaneously, once every 4 weeks for up to 12 weeks. |
| Leuprorelin acetate | DRUG | TAK-385 placebo-matching tablets, orally, once daily and leuprorelin acetate 3.75 mg injection, subcutaneously, once every 4 weeks for up to 12 weeks |
| TAK-385 40 mg | DRUG | TAK-385 40 mg tablet |
| [14C]-TAK-385 Oral Solution | DRUG | TAK-385 oral radiolabelled solution |
| TAK-385 Tablets | DRUG | TAK-385 tablets 2 X 40 mg |
| [14C]-TAK-385 Solution for Intravenous Infusion | DRUG | TAK-385 intravenous (IV) radiolabelled solution |
Inclusion Criteria: 1. Is male, 18 years of age or older. 2. Has histologically confirmed diagnosis of localized prostate adenocarcinoma of intermediate risk for which 6-month neoadjuvant and adjuvant androgen deprivation therapy (ADT) to EBRT is indicated. Intermediate risk per National Comprehens...
TAK-385 is an investigational small molecule being studied for endometriosis, prostate cancer, and uterine fibroids. Clinical trials have evaluated it in Japanese premenopausal healthy adult women and healthy volunteers, as well as in men with prostate cancer. It is in Phase 2 development for these conditions.
TAK-385 is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. The company has sponsored clinical trials of the drug in Japan, the United States, and the United Kingdom.
TAK-385 is in Phase 2 clinical development. It has completed Phase 2 trials for endometriosis and prostate cancer, as well as a Phase 1 food effect study. The drug is investigational and not approved for any use.
TAK-385 has been studied in several completed trials. NCT01452685 and NCT01458301 evaluated it for endometriosis in Japan. NCT02135445 assessed it for localized prostate cancer in the US and UK. NCT02792062 examined food effects in Japanese premenopausal healthy adult women.
TAK-385 is also known as relugolix. It is an oral gonadotropin-releasing hormone receptor antagonist being developed for hormone-dependent conditions such as endometriosis and prostate cancer.
TAK-385 targets the gonadotropin-releasing hormone receptor. By blocking this receptor, it suppresses the release of hormones that stimulate estrogen and testosterone production, which is relevant for treating endometriosis and prostate cancer.