Opko Health Inc (OPK)

[tomsylver]

OPKO (CTAP101) Phase 1 Study For Breast/Prostate Cancer Patients

Effect of CTAP101 Capsules on Ca/iPTH in Advanced Breast/Prostate Cancer Patients Treated With Denosumab/Zoledronic Acid ( http://clinicaltrials.gov/ct2/show/study/NCT02274623 )

Verified November 2014 by OPKO Health, Inc.

Sponsor:
OPKO Ireland Global Holdings Ltd.

Information provided by (Responsible Party):
OPKO Health, Inc. ( OPKO Ireland Global Holdings Ltd. )

ClinicalTrials.gov Identifier:
NCT02274623

First received: October 22, 2014
Last updated: November 5, 2014
Last verified: November 2014

Purpose
This is an open-label exploratory study of CTAP101 Capsules in patients with bone metastases arising from either breast or prostate cancer, who are taking anti-resorptive therapy.

Condition
Breast Cancer
Prostate Cancer
Bone Neoplasms
Hypocalcemia
Hyperparathyroidism, Secondary

Intervention
Drug: CTAP101 Capsules

Phase
Phase 1

Study Type: Interventional
Study Design:
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care

Official Title: Effect of CTAP101 Capsules on Serum Calcium and Plasma Intact Parathyroid Hormone and Vitamin D Metabolites in Patients With Advanced Breast or Prostate Carcinomas With Metastases to Bone and Receiving Ongoing Therapy With Denosumab or Zoledronic Acid

Primary Outcome Measures:

•mean absolute change from baseline for serum calcium [ Time Frame: up to 52 weeks ] [ Designated as safety issue: Yes ]

•mean absolute change from baseline for plasma iPTH [ Time Frame: up to 52 weeks ] [ Designated as safety issue: Yes ]

•mean absolute change from baseline for serum calcifediol [ Time Frame: up to 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

•mean absolute change from baseline for serum phosphorus [ Time Frame: up to 52 weeks ] [ Designated as safety issue: Yes ]

•mean percent change from baseline for fasting spot urine calcium:creatinine [ Time Frame: up to 52 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: November 2014
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)

Arms
Experimental: CTAP101 Capsules
CTAP101 Capsules daily

Assigned Interventions
Drug: CTAP101 Capsules
escalating doses
Other Name: calcifediol

Detailed Description:

This is a multi-center, open-label, repeat-dose study to evaluate the safety, efficacy, and tolerability of CTAP101 Capsules in subjects with bone metastases who are receiving ongoing therapy with denosumab or zoledronic acid. Following screening, approximately 12 eligible subjects with breast cancer and approximately 12 eligible subjects with prostate cancer, all of whom have metastases to bone and are undergoing treatment with anti-resorptive therapies, will receive CTAP101 Capsules at an initial daily oral dose of 30 µg (1 capsule) for 4 weeks. The daily dose may be increased in 30 µg (1 capsule) increments at 4-week intervals to a maximum of 300 µg or until serum calcium reaches >10.3 mg/dL for two consecutive visits (dose escalation phase) at which time the subject will suspend dosing until serum calcium is =10.0 mg/dL and will directly enter a 12-week maintenance phase, resuming treatment at a reduced daily dose, followed by a 2-week follow-up period. Subjects reaching the maximum dose without serum calcium reaching >10.3 mg/dL, will directly enter the 12-week maintenance phase, followed by a 2-week follow-up period. Serum markers for monitoring bone metabolism (including plasma iPTH, PTHrP, and serum free calcifediol), immune function and tumor burden will be measured during the treatment period. The genotype of vitamin D binding protein (DBP) will also be determined. Safety will be monitored through adverse events, serum and urine chemistries, hematology, and ECGs.

Eligibility

Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Criteria
Inclusion Criteria:

•Be diagnosed with bone metastases subsequent to breast (female subjects only) or prostate carcinoma, and will have received zoledronate or denosumab therapy for at least 3 months at the time of enrollment

•Be at least 18 years of age

•Have a life expectancy >12 months from the anticipated time of initiation of treatment

•Serum calcium <9.8 mg/dL

•Plasma iPTH >70 pg/mL

•Estimated glomerular filtration rate (GFR) >15 mL/min/1.73m2

•If taking more than 1000 mg/day of elemental calcium, must be willing and able to discontinue or reduce their calcium use and/or use non-calcium based therapies for the duration of the study

•Subjects receiving =2000 IU/day vitamin D (ergocalciferol or cholecalciferol) therapy must remain on a stable dose during the study. If taking more than 2000 IU/day of vitamin D (ergocalciferol or cholecalciferol), must be willing and able to reduce use to =2000 IU/day and remain on a stable dose for the duration of the study

•Is willing and able to comply with study instructions and commit to all clinic visits for the duration of the study

•Female subject of childbearing potential is neither pregnant nor lactating and must have a negative pregnancy test at the screen visit and a negative pregnancy test before dosing. All female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use effective contraception (eg, implants, injectables, combined oral contraceptives, intrauterine device (IUD), sexual abstinence, vasectomy or vasectomized partner) for the duration of the study

•Has the ability to read and understand subject Informed Consent Form (ICF).

Exclusion Criteria:

•Spot urine Ca:Cr ratio >0.25 (>250 mg/g creatinine)

•Known previous or concomitant serious illness (other than advanced cancer with metastatic bone disease) or medical condition, such as, HIV, significant gastrointestinal disease, or cardiovascular event that in the opinion of the investigator may worsen and/or interfere with participation in the study

•History of neurological/psychiatric disorder, including psychotic disorder or dementia, or any other reason, which in the opinion of the investigator makes adherence to a treatment or follow-up schedule unlikely

•Known or suspected hypersensitivity to any of the constituents of the investigational product

Uncle’s DD Note#

https://opkodd.files.wordpress.com/2014/11/opko-renal1.png&h=230

Ref?

August 7, 2014

OPKO Submits IND for Rayaldee™ as Adjunctive Cancer Therapy ( http://investor.opko.com/releasedetail.cfm?ReleaseID=865077 )

MIAMI--(BUSINESS WIRE)-- OPKO Health, Inc. (NYSE: OPK), announced the submission of an Investigational New Drug (IND) Application to the United States (U.S.) Food and Drug Administration (FDA) under which Rayaldee™ will begin clinical evaluation as an adjunctive therapy for the prevention of skeletal-related events (SREs) in patients with bone metastases undergoing anti-resorptive therapy.

The initial investigation described in this IND is a phase 1 dose titration study designed to evaluate the safety and tolerability of Rayaldee in patients with breast or prostate cancer that has metastasized to bone who are receiving treatment with zoledronic acid (a bisphosphonate) or denosumab (a RANKL inhibitor). Approximately 24 subjects (12 with each cancer type) will receive Rayaldee at a starting daily dose of 30 µg (1 capsule) for 4 weeks. The dose will escalate in 30 µg increments at 4-week intervals until predetermined biochemical endpoints are reached, at which time the subjects will enter a 12-week maintenance phase. Safety parameters and various markers of bone metabolism, immune function and tumor burden will be monitored at regular intervals.

This study is expected to commence later this year and to take approximately 18 months to complete. Following evaluation of this initial study, OPKO plans to conduct subsequent studies investigating the effects of Rayaldee on SREs and other parameters deemed to indicate potential clinical benefits in the targeted population.