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Study in Japan and Ex-Japan to Characterize the Pharmacokinetic and Pharmacodynamic Response to Orteronel (TAK-700) in Chemotherapy-Naïve Patients With Castration-Resistant Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier:
NCT01666314
First received: August 6, 2012
Last updated: September 19, 2016
Last verified: September 2016
  Purpose
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-Naïve Patients With Castration-Resistant Prostate Cancer

Condition Intervention Phase
Prostate Cancer
Drug: Orteronel
Drug: Orteronel Placebo
Drug: Prednisone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Study in Japan and Ex-Japan to Characterize the Pharmacokinetic and Pharmacodynamic Response to Orteronel (TAK-700) in Chemotherapy-Naïve Patients With Castration-Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percentage of Participants with Serum Testosterone Levels Reduced to ≤ 2 ng/dL After 4 Weeks of Treatment in Japan [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants with Serum Testosterone Levels Reduced to ≤ 2 ng/dL in Ex-Japan [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
  • Percent Change from Baseline in Serum Testosterone Level after 4 Weeks of Treatment [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
  • Percent Change from Baseline in Serum Testosterone Level after 12 Weeks of Treatment [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Percentage of Participants with Prostate-Specific Antigen Reduction ≥ 50% (PSA50) after 4 Weeks of Treatment [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
  • Percentage of Participants with PSA50 after 12 Weeks of Treatment [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Absolute Values for Testosterone [ Time Frame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Absolute Values for Dehydroepiandrosterone Sulfate (DHEA-S) [ Time Frame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Absolute Values for Adrenocorticotropic Hormone (ACTH) [ Time Frame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Absolute Values for Corticosterone [ Time Frame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Absolute Values for Cortisol [ Time Frame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Absolute Values for Prostate-Specific Antigen (PSA) [ Time Frame: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Cmax: Maximum Observed Plasma Concentration for Orteronel and M-I Metabolite [ Time Frame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

  • AUC(0-12): Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours Post-dose for Orteronel and M-I Metabolite [ Time Frame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    AUC(0-12) is measure of area under the curve over the dosing interval where the length of the dosing interval is time 0 to 12 hours in this study.

  • Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Orteronel and M-I Metabolite [ Time Frame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

  • AE (0-24) Cumulative Amount of Drug Excreted into the Urine for Orteronel and MI-Metabolite [ Time Frame: Cycle 1 Day 1 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    Cumulative amount of urine excreted time 0 to 24 hour.

  • Cmax,ss: Maximum Observed Plasma Concentration at Steady State for Orteronel and MI-Metabolite [ Time Frame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    Maximum observed steady-state plasma concentration during a dosing interval.

  • 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 [ Time Frame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax at steady state.

  • 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 [ Time Frame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval.

  • Rac: Accumulation index for Orteronel and M-I metabolite [ Time Frame: Cycle 1 Day 8 Predose, 0.5, 1, 2, 3, 5, 8, 12 hours post-dose ] [ Designated as safety issue: No ]
    Rac was calculated as the ratio of AUCtau to AUC12hr.

  • Number of Participants with Adverse events (AEs) and Serious adverse events (SAEs) [ Time Frame: From signing of the informed consent form through 30 days after the last dose of study drug, approximately 2.5 years ] [ Designated as safety issue: Yes ]
    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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding),symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.


Enrollment: 137
Study Start Date: September 2012
Study Completion Date: November 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo + Orteronel 200 mg (Japan)

Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 (28 days) followed by orteronel 200 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 2.5 years.

Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Drug: Orteronel
Orteronel tablets
Drug: Orteronel Placebo
Orteronel placebo-matching tablets
Drug: Prednisone
Prednisone 5 mg
Experimental: Orteronel 200 mg (Japan)

Orteronel 200 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 2.5 years.

Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Drug: Orteronel
Orteronel tablets
Drug: Prednisone
Prednisone 5 mg
Placebo + Orteronel 300 mg (Japan)

Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 followed by orteronel 300 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 2.5 years.

Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Drug: Orteronel
Orteronel tablets
Drug: Orteronel Placebo
Orteronel placebo-matching tablets
Drug: Prednisone
Prednisone 5 mg
Experimental: Orteronel 300 mg (Japan)

Orteronel 300 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 2.5 years.

Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Drug: Orteronel
Orteronel tablets
Drug: Prednisone
Prednisone 5 mg
Placebo + Orteronel 200 mg (Ex-Japan)

Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 followed by orteronel 200 mg, tablets, orally, twice daily in 28 day cycles outside of Japan (Ex-Japan) for up to 2.5 years.

Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Drug: Orteronel
Orteronel tablets
Drug: Orteronel Placebo
Orteronel placebo-matching tablets
Drug: Prednisone
Prednisone 5 mg
Experimental: Orteronel 200 mg (Ex-Japan)

Orteronel 200 mg, tablets, orally, twice daily in 28 day cycles Ex-Japan for up to 2.5 years.

Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Drug: Orteronel
Orteronel tablets
Drug: Prednisone
Prednisone 5 mg
Placebo + Orteronel 400 mg (Ex-Japan)

Orteronel placebo-matching tablets, orally, twice daily in Cycle 1 followed by orteronel 400 mg, tablets, orally, twice daily in 28 day cycles Ex-Japan for up to 2.5 years.

Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Drug: Orteronel
Orteronel tablets
Drug: Orteronel Placebo
Orteronel placebo-matching tablets
Drug: Prednisone
Prednisone 5 mg
Experimental: Orteronel 400 mg (Ex-Japan)

Orteronel 400 mg, tablets, orally, twice daily in 28 day cycles Ex-Japan for up to 2.5.years.

Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Drug: Orteronel
Orteronel tablets
Drug: Prednisone
Prednisone 5 mg

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 patient 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

Patients 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. Patients 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 2.5 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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male patients 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 (eg, 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 [eg, 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01666314

Locations
United States, Nebraska
Urology Cancer Center, PC
Omaha, Nebraska, United States, 68130
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01666314     History of Changes
Other Study ID Numbers: C21013  2012-001539-30  U1111-1179-5750 
Study First Received: August 6, 2012
Last Updated: September 19, 2016
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Takeda:
castrate resistant prostate cancer,
CRPC,
orteronel,
TAK-700

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 30, 2016