Clinical trial NCT01666314: Study in Japan and Ex-Japan to Characterize the Pharmacokinetic and Pharmacodynamic Response to Orteronel (TAK-700) in Chemotherapy-Naive Participants With Castration-Resistant Prostate Cancer
Official title: A Study in Japan and Ex-Japan to Characterize the Pharmacokinetic and Pharmacodynamic Response to Orteronel (TAK-700) in Chemotherapy-Naive Patients With Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: castrate resistant prostate cancer,
CRPC,
orteronel,
TAK-700
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-08-16
Enrollment: 137
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a double-blind, placebo-controlled, multiregional Phase1/2 study to characterize the pharmacokinetic and pharmacodynamic responses to orteronel when administered concomitantly with prednisone in Chemotherapy-Naive Participants With Castration-Resistant Prostate Cancer

Detailed description: The drug being tested in this study is called orteronel. Orteronel is being tested to treat adult males who have adenocarcinoma of the prostate. This study will look at the pharmacokinetics (how the drug moves through the body) and pharmacodynamics (how the drug effects the body) in people who take orteronel in addition to prednisone.

The study will enroll approximately 144 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the eight treatment groups (4 in Japan, 4 in Ex-Japan) which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).

In Japan:

Participants were randomized in a ratio of 2:1:2:1

* 200 mg orteronel or Placebo-matching orteronel \[(dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient\] twice daily (BID) + prednisone
* 300 mg orteronel, or Placebo-matching orteronel, BID + prednisone Ex-Japan Participants were randomized in a ratio of 2:1:2:1
* 200 mg orteronel or Placebo-matching orteronel, BID in Cycle 1 + prednisone
* 400 mg orteronel, or Placebo-matching orteronel ,BID in Cycle 1 + Prednisone

Participants initially randomized to placebo received 4 weeks of placebo and then 12 weeks of active treatment with orteronel then entered a follow-up period treatment period. Participants initially randomized to orteronel received 16 weeks of treatment then entered a follow-up treatment period.

This multi-centre trial will be conducted worldwide. The overall time to participate in this study is approximately 3.2 years. Participants will make multiple visits to the clinic and a final visit 30 to 40 days after receiving their last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

* Male participants 18 years or older
* Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
* Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma
* Prior surgical castration or concurrent use of an agent for medical castration \[e.g. Gonadotropin-releasing hormone (GnRH) analogue\]
* Prostate-Specific Antigen (PSA) ≥ 2 ng/mL at screening
* Progressive disease based on PSA and/or radiographic criteria

Exclusion Criteria:

* Prior therapy with orteronel, ketoconazole, aminoglutethimide, or abiraterone.
* Known hypersensitivity to compounds related to orteronel, orteronel excipients, prednisone (or commercially available equivalent), or GnRH analogue.
* All antiandrogen therapy (including bicalutamide) is excluded within 4 weeks before the first dose of study drug. Any other therapies for prostate cancer, other than GnRH analogue therapy, such as progesterone, medroxyprogesterone, progestins (megesterol), or 5- alpha reductase inhibitors (e.g., finasteride or dutasteride), must be discontinued 2 weeks before the first dose of study drug.
* Continuous daily use of oral prednisone (or commercially available equivalent), oral dexamethasone, or other systemic corticosteroids for more than 2 weeks within the 3 months before screening (inhaled, nasal, and local steroids \[e.g., joint injection\] are allowed).
* Prior chemotherapy for prostate cancer, with the exception of neoadjuvant/adjuvant therapy as part of initial primary treatment for local disease that was completed 2 or more years before screening.

Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons.

Primary outcomes:
measure: Percentage of Participants With Serum Testosterone Levels Reduced to ≤ 2 ng/dL After 4 Weeks of Treatment in Japan
timeFrame: Baseline and Week 4
Secondary outcomes:
measure: Percentage of Participants With Serum Testosterone Levels Reduced to ≤ 2 ng/dL in Ex-Japan
timeFrame: Baseline and Week 4
measure: Percent Change From Baseline in Serum Testosterone Level After 4 Weeks of Treatment
timeFrame: Baseline and Week 4
measure: Percent Change From Baseline in Serum Testosterone Level After 12 Weeks of Treatment
timeFrame: Baseline and Week 12
measure: Percentage of Participants With Prostate-Specific Antigen Reduction ≥ 50% (PSA50) After 4 Weeks of Treatment
timeFrame: Baseline and Week 4
measure: Percentage of Participants With PSA50 After 12 Weeks of Treatment
timeFrame: Baseline and Week 12
measure: Absolute Values for Testosterone
timeFrame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1
measure: Absolute Values for Dehydroepiandrosterone Sulfate (DHEA-S)
timeFrame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1
measure: Absolute Values for Adrenocorticotropic Hormone (ACTH)
timeFrame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1
measure: Absolute Values for Corticosterone
timeFrame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1
measure: Absolute Values for Cortisol
timeFrame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1
measure: Absolute Values for Prostate-Specific Antigen (PSA)
timeFrame: Baseline and Cycle 2 Day 1
measure: Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite
timeFrame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose
measure: AUC(0-12): Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours Post-dose for Orteronel and M-I Metabolite
timeFrame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite
timeFrame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose
measure: AE (0-24) Cumulative Amount of Drug Excreted Into the Urine for Orteronel and MI-Metabolite
timeFrame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose
measure: Cmax,ss: Maximum Observed Plasma Concentration at Steady State for Orteronel and MI-Metabolite
timeFrame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose
measure: Tmax,ss: Time to Reach the Maximum Plasma Concentration (Cmax), Equal to Time (Hours) to Cmax at Steady State for Orteronel and M-I Metabolite
timeFrame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose
measure: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Orteronel and M-I Metabolite
timeFrame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose
measure: Rac: Accumulation Index for Orteronel and M-I Metabolite
timeFrame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose
measure: Ctrough,ss: Observed Predose Plasma Concentration at Steady State for Orteronel and M-I Metabolite
timeFrame: Cycle 1 Day 8 Predose
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From signing of the informed consent form through 30 days after the last dose of study drug, approximately 3.2 years
Other outcomes:
Locations:
city: Omaha
country: United States
facility: Urology Cancer Center, PC
state: Nebraska
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: