Safety and Efficacy of CTAP101 Capsules to Treat Secondary Hyperparathyroidism in Stage 3 or 4 CKD and Vitamin D Insufficiency

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
OPKO Health, Inc. ( OPKO IP Holdings II, Inc. )
ClinicalTrials.gov Identifier:
NCT01651000
First received: July 23, 2012
Last updated: March 28, 2016
Last verified: March 2016
  Purpose
This study will evaluate the efficacy of CTAP101 Capsules versus placebo in reducing intact parathyroid hormone (iPTH) by at least 30% from pretreatment baseline; safety and tolerability of CTAP101 will also be evaluated

Condition Intervention Phase
Chronic Kidney Disease
Hyperparathyroidism, Secondary
Vitamin D Deficiency
Drug: CTAP101 30 μg capsules
Drug: CTAP101 60 μg capsules
Drug: CTAP101 30 μg sugar pill capsule
Drug: CTAP101 60 μg sugar pill capsules
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of CTAP101 Capsules to Treat Secondary Hyperparathyroidism in Subjects With Stage 3 or 4 Chronic Kidney Disease and Vitamin D Insufficiency

Resource links provided by NLM:


Further study details as provided by OPKO Health, Inc.:

Primary Outcome Measures:
  • Changes of at least 30% in plasma iPTH from pretreatment baseline [ Time Frame: Approximately 6 months ] [ Designated as safety issue: No ]

    Primary Objectives:

    The primary objectives of this study are:

    To evaluate the efficacy of CTAP101 Capsules versus placebo in reducing plasma intact parathyroid hormone (iPTH) by at least 30% from pre-treatment baseline


  • Changes in safety and tolerability to CTAP101 capsules [ Time Frame: Approximately 6 months ] [ Designated as safety issue: Yes ]
    To investigate the safety and tolerability of CTAP101 Capsules through changes in adverse events, physical examinations,vital signs, clinical laboratory tests, vital signs, and 12-lead ECGs


Secondary Outcome Measures:
  • Changes in serum total 25D to ≥ 30 ng/ML [ Time Frame: Approximately 6 months ] [ Designated as safety issue: No ]
    To evaluate the efficacy of CTAP101 capsules versus placebo in increasing serum total 25D to ≥ 30 ng/ML

  • Changes in hypercalciuria, hypercalcemia and drug-related hyperphosphatemia. [ Time Frame: Approximately 6 months ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Changes in efficacy and safety based on weight, age, gender, race, dose, CKD stage, SHPT severity, use of Vitamin D supplements, use of Ca supplements, baseline serum total 25D and eGFR [ Time Frame: Approximately 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 213
Study Start Date: September 2012
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CTAP101 30 μg capsules
1 CTAP101 30 μg capsule daily at bedtime
Drug: CTAP101 30 μg capsules
Subjects will take 1 capsule (CTAP101 30 μg) daily at bedtime for 12 weeks. After 12 weeks, the dose may be increased in a blinded fashion based on dose titration criterion. Subjects not requiring a dose increase would receive one CTAP101 30 μg capsule plus one placebo (30 μg sugar pill capsule) for 30 μg total dose.
Other Name: Calcifediol
Active Comparator: CTAP101 60 μg capsules
2 CTAP101 30 μg capsules daily at bedtime
Drug: CTAP101 60 μg capsules
Subjects will take 1 capsule (CTAP101 30 μg) daily at bedtime for 12 weeks. After 12 weeks, the dose may be increased in a blinded fashion based on dose titration criterion. Subjects requiring a dose increase would receive two CTAP101 30 μg capsules (60 μg total dose).
Other Name: Calcifediol
Placebo Comparator: CTAP101 30 μg sugar pill capsule
1 CTAP101 sugar pill capsule daily at bedtime
Drug: CTAP101 30 μg sugar pill capsule
Subjects will take 1 capsule (CTAP101 30 μg matching placebo; 1 CTAP101 sugar pill capsule) daily at bedtime for 12 weeks. After 12 weeks, the dose may be increased in a blinded fashion based on dose titration criterion. Subjects would receive two CTAP101 matching placebo capsules (two CTAP 30 μg sugar pill capsules).
Other Name: Placebo
Placebo Comparator: CTAP101 60 μg sugar pill capsules
2 CTAP101 30 μg sugar pill capsules daily at bedtime
Drug: CTAP101 60 μg sugar pill capsules
Subjects will take 1 capsule (CTAP101 30 μg matching placebo; 1 CTAP101 sugar pill capsule) daily at bedtime for 12 weeks. After 12 weeks, the dose may be increased in a blinded fashion based on dose titration criterion. Subjects would receive two CTAP101 matching placebo capsules (two CTAP 30 μg sugar pill capsules).
Other Name: Placebo

Detailed Description:
This is a phase 3, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of CTAP101 Capsules administered for 26 weeks to treat SHPT in subjects ≥18 years of age with stage 3 or 4 CKD and vitamin D insufficiency. The study will be conducted at approximately 40 sites within the United States (US). Approximately 550 subjects will be screened to randomize approximately 210 eligible subjects, stratified by CKD stage (approximately 105 subjects in each stage) in a 2:1 ratio to receive either CTAP101 Capsules or matching placebo. An Interactive Voice Response System (IVRS) will provide study treatment group assignments using the computer-generated randomization code provided by the IVRS vendor. Subjects will receive an initial daily dose of 1 capsule (CTAP101 Capsules, 30 µg, or matching placebo) for the first 12 weeks. After l2 weeks (visit 8) and per pre-defined criteria, the dose may be increased in a blinded fashion by the IVRS with oversight by an independent medical monitor.
  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Urinary albumin excretion ≤ 3000 mcg/mg of creatinine
  2. Stage 3 or 4 CKD
  3. Plasma iPTH: ≥ 85 pg/mL and < 500 pg/mL
  4. Serum Ca: ≥ 8.4 mg/dL and < 9.8 mg/dL
  5. Serum P: ≥ 2.0 mg/dL and < 5.0 mg/dL
  6. Serum 25-hydroxyvitamin D: ≥ 10 ng/mL and < 30 ng/mL.
  7. Stable dose of Vitamin D therapy ≤ 1600 IU/day and receiving same dose for at least 2 months

Exclusion Criteria:

  1. History of kidney transplant or parathyroidectomy
  2. Spot urine calcium:creatinine ratio > 0.2 (>200 mg/g Cr)
  3. Current serious illness, such as malignancy, HIV, liver disease, cardiovascular event or hepatitis
  4. Currently on dialysis
  5. Use of pharmacological dose of ergocalciferol or cholecalciferol (≥ 50,000 IU mcg per month) during the study
  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: NCT01651000

Locations
United States, Illinois
OPKO Renal
Bannockburn, Illinois, United States, 60015
Sponsors and Collaborators
OPKO IP Holdings II, Inc.
Investigators
Study Director: Joel Melnick, MD Opko Renal
  More Information

Responsible Party: OPKO Health, Inc. ( OPKO IP Holdings II, Inc. )
ClinicalTrials.gov Identifier: NCT01651000     History of Changes
Other Study ID Numbers: CTAP101-CL-3001 
Study First Received: July 23, 2012
Last Updated: March 28, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by OPKO Health, Inc.:
Parathyroid Diseases
Renal Insufficiency
Kidney Failure, Chronic
Hyperparathyroidism, Secondary
Vitamin D
Hyperparathyroidism
Kidney Diseases
Kidney Failure
Renal Insufficiency, Chronic

Additional relevant MeSH terms:
Hyperparathyroidism
Hyperparathyroidism, Secondary
Kidney Diseases
Neoplasm Metastasis
Renal Insufficiency, Chronic
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Endocrine System Diseases
Malnutrition
Neoplasms
Neoplastic Processes
Nutrition Disorders
Parathyroid Diseases
Pathologic Processes
Renal Insufficiency
Urologic Diseases
Calcifediol
Contraceptives, Oral
Vitamin D
Bone Density Conservation Agents
Contraceptive Agents
Contraceptive Agents, Female
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses
Vitamins

ClinicalTrials.gov processed this record on May 02, 2016