Primary objective:* To determine whether orteronel 300 mg twice daily (BID) plus prednisone 5 mg BID more effectively reduces serum testosterone levels, compared to placebo plus prednisone 5 mg BID, when administered to patients in JapanSecondary…
ID
Source
Brief title
Condition
- Reproductive neoplasms male benign
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
* Percentage of patients in Japan with serum testosterone levels reduced to * 2
ng/dL after 4 weeks of treatment with orteronel 300 mg BID plus prednisone 5 mg
BID, when compared to placebo plus prednisone 5 mg BID
Secondary outcome
Secondairy endpoints:
* Percentage of ex-Japan patients with serum testosterone levels reduced to * 2
ng/dL after 4 weeks of treatment with orteronel 400 mg BID plus prednisone 5 mg
BID, when compared to placebo plus prednisone 5 mg BID
* Serum testosterone levels after 4 weeks of treatment with study drug
(orteronel plus prednisone or placebo plus prednisone) and after 12 weeks of
active treatment with orteronel plus prednisone in all treatment groups
Background summary
As a selective, nonsteroidal inhibitor of 17,20-lyase, a key intermediary in
the testosterone synthesis pathway, orteronel is currently in clinical
development as a treatment for men with CRPC, where persistent extragonadal
synthesis of androgens in the adrenal cortex or possibly in tumor cells results
in sustained tumor stimulation and progression.
This is a randomized, double-blind, placebo-controlled, multiregion study in
Japan and ex Japan to characterize the PK and pharmacodynamic responses to
orteronel, when administered concomitantly with prednisone, in adult men with
CRPC. The primary objective of this study is to determine whether orteronel
300 mg BID plus prednisone 5 mg BID more effectively reduces serum testosterone
levels, compared to placebo plus prednisone 5 mg BID, when administered to
patients in Japan. Pharmacokinetic and pharmacodynamic data will be collected
from patients in Japan and ex-Japan to establish an orteronel dose for patients
in Japan that has similar exposure to the global dose for orteronel.
Please refer to section 1.4 of the protocol.
Study objective
Primary objective:
* To determine whether orteronel 300 mg twice daily (BID) plus prednisone 5 mg
BID more effectively reduces serum testosterone levels, compared to placebo
plus prednisone 5 mg BID, when administered to patients in Japan
Secondary objectives:
* To evaluate the reduction in serum testosterone levels in ex-Japan patients
administered orteronel 400 mg BID plus prednisone 5 mg BID, when compared to
placebo plus prednisone 5 mg BID
* To determine whether orteronel plus prednisone improves 50% prostate-specific
antigen (PSA) response
* To evaluate the effect of orteronel plus prednisone on endocrine markers of
pharmacodynamic response
* To characterize the pharmacokinetics of orteronel plus prednisone
* To continue to assess the safety of orteronel plus prednisone in patients
with castration resistant prostate cancer (CRPC)
Exploratory objective:
* To explore the pharmacokinetic (PK) -pharmacodynamic response to orteronel
plus prednisone in patients in Japan and ex-Japan
Study design
This is a double-blind, placebo-controlled, multiregion study in Japan and
ex-Japan to characterize the PK and pharmacodynamic responses to orteronel when
administered concomitantly with prednisone.
Following the Screening period, patients will be randomized to receive study
drug (orteronel or placebo) BID in a double-blind fashion.
Serial blood and urine samples for PK analysis of the study drug and
metabolite(s) will be collected at the time points specified.
At Cycle 2, Day 1, patients randomized to placebo will receive active treatment
with orteronel at the initially assigned dose level. Patients already
randomized to active treatment with orteronel will continue to receive their
current dose level.
After completing Cycle 5, Day 1 assessments, patients may enter the follow-up
portion of the study. Patients may remain on treatment at the discretion of
the investigator and treated according to the standard of care, returning to
the site for follow-up visits at the time points specified.
Intervention
Patients in Japan will be randomized to receive orteronel 200 mg BID, orteronel
300 mg BID, or placebo (placebo in Cycle 1 only). Ex Japan patients will be
randomized to receive orteronel 200 mg BID, orteronel 400 mg BID, or placebo
(placebo in Cycle 1 only). Study drug will be administered concomitantly with
prednisone (or commercially available equivalent) 5 mg BID continuously
throughout the study.
Study burden and risks
For a complete overview of the procedures please refer to the *schedule of
events* in the protocol.
The patients will have to take the study medication and prednisone twice per
day on set timepoint.
There is an extended farmacokinetic and farmacodynamic research related to this
study.
Patients will be asked to complete a medication diary during the active
treatment period (first 4 cycles). Herein they note the timepoint of a meal
before intake of the study medication and the timepoint of intake of Orteronel
and prednisone. No questionnaires will be completed.
Patients receiving Orteronel noted the following side effects:
Feeling tired, headache, high aminotransferases, decline of LVEF, itching and
rash, worsening performance, worsening but controlled hypertension, episodic
nausea, vomiting, diarrhea, and dehydration (see IB for more detailed about
safety). Until now the identified risks related to oreteronel treatment:
nausea, vomiting, feeling tired, hypertension, rash, and androgen deprivation.
Some laboratory tests on the study drug (TAK-700) showed that one breakdown
product of the study drug (TAK-700) may have activity that could cause an
undesired change in the genes or chromosomes. This potential change could
increase the risk of developing a secondary cancer in addition to the prostate
cancer. If a genetic or chromosomal change happens in the sperm and the
patient does father a baby, the change could be passed on to the child and
could have an adverse effect on the developing fetus. Studies to see if this
potential genetic or chromosomal change occurs in animals have not been
conducted and the effect in humans from activity of the breakdown product is
not known.
Landsdowne Street 40
Cambridge, Masachussets MA 02139
US
Landsdowne Street 40
Cambridge, Masachussets MA 02139
US
Listed location countries
Age
Inclusion criteria
1. Male patients 18 years or older.
2. 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.
3. Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma.
4. Prior surgical castration or concurrent use of an agent for medical castration (eg, GnRH analogue).
5. PSA * 2 ng/mL at screening.
6. Progressive disease based on PSA and/or radiographic criteria.
Exclusion criteria
1. Prior therapy with orteronel, ketoconazole, aminoglutethimide, or abiraterone.
2. Known hypersensitivity to compounds related to orteronel, orteronel excipients, prednisone (or commercially available equivalent), or GnRH analogue.
3. 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.
4. 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).
5. 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-001539-30-NL |
| ClinicalTrials.gov | NCT01666314 |
| CCMO | NL40913.060.12 |