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

Millennium Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Prostate Cancer

Treatments: Drug: Orteronel Placebo; Drug: Prednisone; Drug: Orteronel

Study type: Interventional

Funder types: Industry

Identifiers

NCT01666314

C21013

U1111-1179-5750 (Other Identifier)

2012-001539-30 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 137 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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137 participants in 8 patient groups

Placebo + Orteronel 200 mg (Japan)

Other group

Description:

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

Treatment:

Drug: Prednisone

Drug: Orteronel

Drug: Orteronel Placebo

Orteronel 200 mg (Japan)

Experimental group

Description:

Orteronel 200 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 3 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Treatment:

Drug: Prednisone

Drug: Orteronel

Placebo + Orteronel 300 mg (Japan)

Other group

Description:

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

Treatment:

Drug: Prednisone

Drug: Orteronel

Drug: Orteronel Placebo

Orteronel 300 mg (Japan)

Experimental group

Description:

Orteronel 300 mg, tablets, orally, twice daily in 28 day cycles in Japan for up to 2.8 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Treatment:

Drug: Prednisone

Drug: Orteronel

Placebo + Orteronel 200 mg (Ex-Japan)

Other group

Description:

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

Treatment:

Drug: Orteronel

Orteronel 200 mg (Ex-Japan)

Experimental group

Description:

Orteronel 200 mg, tablets, orally, twice daily in 28 day cycles Ex-Japan for up to 3.1 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Treatment:

Drug: Prednisone

Drug: Orteronel

Placebo + Orteronel 400 mg (Ex-Japan)

Other group

Description:

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

Treatment:

Drug: Prednisone

Drug: Orteronel

Drug: Orteronel Placebo

Orteronel 400 mg (Ex-Japan)

Experimental group

Description:

Orteronel 400 mg, tablets, orally, twice daily in 28 day cycles Ex-Japan for up to 3.1 years. Study drug will be administered concomitantly with prednisone (or commercially available equivalent) 5 mg twice daily (BID) continuously throughout the study.

Treatment:

Drug: Prednisone

Drug: Orteronel