Study in Men With Prostate Cancer to Assess the Safety, Pharmacokinetics and Testosterone-Lowering Efficacy of TAK-448

NCT01132404 | Terminated Phase 1

• 2 other identifiers: C180022009-017668-18
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The phase 1 portion of this study is an open-label, multicenter, dose-escalation study of 1-month depot TAK-448 in adult males with prostate cancer who are either on gonadotropin releasing hormone (GnRH) therapy or who might be eligible for GnRH therapy in the future. The phase 2 portion of this study is an open-label, multicenter, randomized study in men with prostate cancer that will confirm the testosterone- and prostate specific antigen (PSA)- lowering potential of up to 2 dose levels of 1-month depot TAK-448.

Conditions

Prostate Cancer; Prostatic Neoplasms

Outcome Measures

Primary Outcomes (2)

• For Phase 1 portion of study: to assess the safety and pharmacokinetics (PK) of TAK-448 in patients receiving a single dose of 1-month depot TAK-448

  Vital signs; 12-lead ECG; Clinical laboratory test results; Injection site-related skin reactions; Adverse Events (AEs)and Serious Adverse Events (SAEs); Maximum observed plasma concentration; Area under the plasma TAK-448 disposition curve; The time of last quantifiable concentration

  3 months

• For Phase 2 portion of study: to assess the safety and PK of TAK-448 and effect of TAK-448 on serum testosterone concentrations in patients receiving repeated doses of 1-month depot TAK-448

  Vital signs; 12-lead ECG; Clinical laboratory test results; Injection site-related skin reactions; Adverse Events (AEs)and Serious Adverse Events (SAEs; Area under the plasma TAK-448 disposition curve; trough plasma concentration; Serum testosterone concentration; proportion of patients with serum concentration below castrate level

  8 months

Secondary Outcomes (2)

• For Phase 1 portion of study: to assess the effect of 1-month depot TAK-448 on serum testosterone and luteinizing hormone (LH) concentrations in patients not receiving concomitant gonadotropin releasing hormone (GnRH) analog therapy

  3 months

• For Phase 2 portion of study: to assess the effect of 1-month depot TAK-448 on serum prostate specific antigen (PSA) concentration

  8 months

Study Arms (3)

TAK-448 Dose 1

EXPERIMENTAL

Drug: TAK-448

TAK-448 Dose 2

EXPERIMENTAL

Drug: TAK-448

Leuprorelin

ACTIVE COMPARATOR

Drug: Leuprorelin

Interventions

Leuprorelin DRUG

Phase 2 portion of study: patients randomized to this arm will receive a subcutaneous injection of depot Leuprorelin in the abdomen once per month for up to 6 months

Leuprorelin

TAK-448 DRUG

Phase 1 portion of study: Patients will be administered a single dose of depot formulation TAK-448 via subcutaneous abdominal injection and a single dose of placebo at a contralateral injection site Phase 2 portion of the study: Patients randomized to this arm will be administered depot formulation TAK-448 (up to 2 dose levels) via subcutaneous injection in the abdomen once per month for up to 6 months

TAK-448 Dose 1; TAK-448 Dose 2

Eligibility Criteria

• Age: 40 Years - 72 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male 40 to 72 years of age
• Histologically-confirmed adenocarcinoma of the prostate having completed primary local treatment at least 6 months prior to screening
• Meet all laboratory evaluation values at screening as specified in protocol
• For phase 1 of the study only: Concurrent gonadotropin releasing hormone (GnRH) therapy with generally indolent or stable disease OR a potential candidate of GnRH at some time in the future. Patients with metastatic disease must be asymptomatic with only bone scan positive evidence of metastases. Patients with recurrent local disease will be asymptomatic without bladder, bowel or obstructive symptoms
• For phase 2 portion of the study only: evidence of progressive prostate cancer, which in the opinion of the referring physician and/or study investigator warrants the initiation of GnRH analog therapy. Such patients may have either elevated or rising PSA at least 6 months following primary local therapy (ies) or have evidence of metastatic disease not previously treated with GnRH analog therapy.
• Provision of informed consent and for the phase 1 portion of the study only, willing to participate with no expectation of therapeutic benefit
• Generally fit medical condition, with no acute or chronic medical conditions other than prostate cancer, affecting 2-year life expectancy
• Ability to understand and comply with protocol requirements
• Agreement to, even if surgically sterilized but not surgically castrated, practice effective barrier contraception OR abstain from heterosexual intercourse
• Suitable venous access for blood sampling

You may not qualify if:

• Advanced or symptomatic metastatic prostate cancer requiring immediate GnRH or additional hormone therapy or requiring chemotherapy
• History of surgical castration
• History of nonskin cancer, other than prostate cancer, requiring active treatment within 2 years of screening
• History of cardiac surgery, within the previous 6 months or any planned elective surgeries, other than skin surgery, during the ensuing 6 months
• Compromise of bone marrow function that would reduce tolerance to repeated blood draws
• History of osteoporosis, unless actively controlled with treatment, or history of vertebral or femoral fracture within the past year
• History of seizures or currently on anticonvulsant medications
• History of major psychiatric illness (diagnosed psychosis or psychiatric illness requiring hospitalization)
• History of drug or significant alcohol abuse
• Participation in clinical trials or receipt of experimental therapy within 2 months of screening
• Serious infection within 14 days before first dose of study drug
• Known history of human immunodeficiency (HIV) infection, hepatitis B, or hepatitis C infection
• History of significant cardiovascular condition
• Participation in the phase 1 portion of the study
• Prior or current use of a GnRH analog or androgen receptor antagonist as first-line hormone therapy (other than as neoadjuvant/adjuvant use)

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (1)

Hôpital Edouard Herriot, 5, Place d'Arsonval, Pavillon V - Urologie et chirurgie de la transplantation

Lyon, 69437, France

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Leuprolide; metastin (46-54), acetyl-tyrosyl(46)-hydroxypropyl(47)-threonyl(49)-azaglycyl(51)-methylarginyl(53)-tryptophyl(54)-

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2010
• First Posted: May 28, 2010
• Study Start: November 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: December 1, 2011
• Last Updated: January 31, 2012

Record last verified: 2012-01

Locations

FR (1)