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

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

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

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency; Chronic Kidney Disease; Hyperparathyroidism, Secondary
• Intervention / Treatment: Drug: CTAP101 30 μg capsules; Other: Sugar pill to CTAP101 30 μg capsules

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.

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Bannockburn, Illinois, United States, 60015
      • OPKO Renal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CTAP101 30 μg capsules; 1 CTAP101 30 μg capsule daily at bedtime for 12 weeks, with a possible increase to 2 CTAP101 30 μg capsules daily at bedtime for study duration, if needed (26 weeks total). Subjects not requiring a dose increase after 12 weeks would receive 1 CTAP101 30 μg capsule and one sugar pill (to CTAP101 30 μg capsule) for weeks 13-26.	Drug: CTAP101 30 μg capsules; CTAP101 30 μg capsule taken daily at bedtime; Other Names: Calcifediol; Other: Sugar pill to CTAP101 30 μg capsules; Sugar pill capsule (placebo to CTAP101 30 μg capsule) taken daily at bedtime.; Other Names: Placebo
Placebo Comparator: Sugar pill to CTAP101 30 μg; 1 sugar pill to CTAP101 30 μg capsule daily at bedtime for 12 weeks, with an increase to 2 sugar pills to CTAP101 30 μg capsules daily at bedtime for weeks 13-26.	Other: Sugar pill to CTAP101 30 μg capsules; Sugar pill capsule (placebo to CTAP101 30 μg capsule) taken daily at bedtime.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants in the Intent to Treat Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline	Number of subjects in the intent to treat population attaining mean decrease in plasma intact Parathyroid Hormone (iPTH) of ≥30% from P\pre-treatment baseline in the efficacy assessment phase (EAP) referred to as responders	Approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants in the Per Protocol Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline	Number of subjects in the per protocol population attaining a mean decrease in plasma intact parathyroid hormone (iPTH) of ≥30% from pre-treatment baseline in the efficacy assessment phase (EAP), referred to as responders	Approximately 6 months
Subjects in the Intent to Treat Population With Normal Serum Total 25-hydroxyvitamin D	Subjects in the intent to treat population with normal serum total 25-hydroxyvitamin D (>/= 30 ng/dL)	Approximately 6 months
Subjects in the Per Protocol Population With Normal Serum Total 25-hydroxyvitamin D	Subjects in the per protocol population with normal serum total 25-hydroxyvitamin D (>/= 30 ng/mL)	Approximately 6 months

Collaborators and Investigators

• Sponsor: OPKO IP Holdings II, Inc.
• Investigators: Study Director: Joel Melnick, MD, OPKO Renal

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: October 6, 2012
• First Submitted That Met QC Criteria: October 9, 2012
• First Posted (Estimate): October 11, 2012

Study Record Updates

• Last Update Posted (Actual): December 18, 2019
• Last Update Submitted That Met QC Criteria: December 17, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Vitamin D; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Kidney Failure; Parathyroid Diseases; Hyperparathyroidism, Secondary; Hyperparathyroidism
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Nutrition Disorders; Parathyroid Diseases; Neoplastic Processes; Avitaminosis; Deficiency Diseases; Malnutrition; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Neoplasm Metastasis; Vitamin D Deficiency; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcifediol
• Other Study ID Numbers: CTAP101-CL-3002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No