CKD Stage 3, CKD Stage 4, Secondary Hyperparathyroidism Due to Renal Causes, Vitamin D Insufficiency
Conditions
Brief summary
An Open-Label, Repeated-Dose Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Study of Oral CTAP101 Capsules, Immediate- Release (IR) Calcifediol, High-Dose Cholecalciferol, and Paricalcitol Plus Low-Dose Cholecalciferol in Patients with Secondary Hyperparathyroidism, Stage 3 or 4 Chronic Kidney Disease and Vitamin D Insufficiency
Interventions
Capsule, daily
DRUGCalcifediol Oral Product
Capsule, once a month
DRUGCholecalciferol
Capsule, once a month
DRUGParicalcitol Oral Capsule
Capsule, daily
Sponsors
OPKO Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be at least 18 years of age. 2. Have stage 3 or 4 CKD (estimated glomerular filtration rate \[eGFR\] of ≥15 to \<60 millilter per minute per 1.73 meter square (mL/min/1.73 m2) using the Modification of Diet in Renal Disease equation). 3. Be without any disease state or physical condition that might impair evaluation of safety and efficacy or which, in the Investigator's opinion, would interfere with study participation, including: 1. Serum albumin ≤ 3.0 (grams per deciliter (g/dL); 2. Serum transaminase (alanine transaminase, glutamic pyruvic transaminase, aspartate aminotransferase or glutamic oxaloacetic transaminase) \> 2.5 times the upper limit of normal at screening; and, 3. Urinary albumin excretion ≤3000 microgram per milligram (μg/mg) creatinine. 4. Exhibit during the initial screening visit: 1. Plasma intact parathyroid hormone (iPTH) ≥70 picogram per milliliter (pg/mL) and \<400 pg/mL if receiving calcitriol or other 1α- hydroxylated vitamin D analog (paricalcitol or doxercalciferol); or 2. Plasma iPTH ≥100 pg/mL and \<500 pg/mL if not receiving calcitriol or other 1α- hydroxylated vitamin D analog; and, 3. Serum total 25-hydroxyvitamin D \<30 nanogram per milliliter (ng/mL). 5. If taking calcitriol, other 1α-hydroxylated vitamin D analog, or vitamin D supplementation, must forgo treatment with these non-study agents for the duration of the study and undergo a 4-week washout period. 6. Exhibit after the 4-week washout period (if required): 1. Plasma iPTH ≥100 pg/mL and \<500 pg/mL; 2. Corrected serum calcium \<9.8 mg/dL; (corrected for serum albumin) 3. Serum total 25-hydroxyvitamin D \<30 nanogram per milliliter (ng/mL); and, 4. Serum phosphorus \<5.5 milligram per deciliter (mg/dL). 7. If taking more than 1,500 milligram per day (mg/day) of elemental calcium, reduce calcium use (to approximately 1,000 to ≤1,500 mg/day) for the duration of the study. 8. Willing and able to comply with study instructions and commit to all clinic visits for the duration of the study. 9. Female subjects of childbearing potential must be neither pregnant nor lactating and must have negative blood pregnancy tests at the first screening visit. 10. All female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use effective contraception (implants, injectables, combined oral contraceptives, intrauterine device, sexual abstinence, vasectomy or vasectomized partner) for the duration of the study. 11. Be able to read, understand and sign the subject Informed Consent Form (ICF) or have a legal authorized representative (LAR) sign the ICF.
Exclusion criteria
1. History of or planned kidney transplant or parathyroidectomy 2. History (prior 3 months) of corrected serum calcium ≥9.8 mg/dL or serum phosphorus ≥5.5 mg/dL if not receiving calcitriol or other 1α-hydroxylated vitamin D analog. 3. Need for phosphate binders to maintain the serum phosphate \< 5.5 mg/dL or use of phosphate binders within 4 weeks prior to screening 4. Use of calcimimetic therapy (cinacalcet or etelcalcetide) within 12 weeks of screening. 5. Receipt of bisphosphonate therapy or other bone modifying treatment within 6 months prior to enrollment. 6. Known previous or concomitant serious illness or medical condition, such as malignancy, human immunodeficiency virus, significant gastrointestinal or hepatic disease, intestinal malabsorption disorder, hepatitis or cardiovascular event that in the opinion of the Investigator may worsen or reduce life expectancy, and/or interfere with participation in the study. 7. History of neurological/psychiatric disorder, including psychotic disorder or dementia, or any reason which, in the opinion of the Investigator makes adherence to a treatment or follow-up schedule unlikely. 8. Known or suspected hypersensitivity to any of the constituents of the study drugs. 9. Currently participating in, or has participated in, an interventional/investigational study within 30 days prior to study screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | 5 months | This study is descriptive and no primary or secondary efficacy endpoints are defined. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CTAP101 CTAP101/Calcifediol Capsules 60 micrograms (mcg) once daily at bedtime, except on Days 1 and 29 when dosing will occur in the morning before breakfast
Calcifediol Oral Capsule: Capsule, daily | 18 |
| Immediate-release (IR) Calcifediol Immediate-release (IR) calcifediol/266 micrograms (mcg) capsule before breakfast on the mornings of Day 1 and Day 29
Calcifediol Oral Product: Capsule, once a month | 18 |
| Cholecalciferol Cholecalciferol/Capsules 300,000 International Units (IU) (high-dose) before breakfast on the mornings of Day 1 and Day 29
Cholecalciferol: Capsule, once a month | 18 |
| Paricalcitol Paricalcitol/Capsules 1 mcg plus cholecalciferol capsules 800 IU (low-dose) once daily in the morning before breakfast, except on Days 1 and29 when dosing will occur before breakfast
Cholecalciferol: Capsule, once a month
Paricalcitol Oral Capsule: Capsule, daily | 15 |
| Total | 69 |
Baseline characteristics
| Characteristic | CTAP101 | Immediate-release (IR) Calcifediol | Cholecalciferol | Paricalcitol | Total |
|---|---|---|---|---|---|
| Age, Continuous | 67.1 Year STANDARD_DEVIATION 10.7 | 70.1 Year STANDARD_DEVIATION 14.4 | 67.9 Year STANDARD_DEVIATION 9.8 | 63.4 Year STANDARD_DEVIATION 12 | 67.3 Year STANDARD_DEVIATION 11.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 17 Participants | 17 Participants | 14 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 5 Participants | 10 Participants | 32 Participants |
| Sex: Female, Male Male | 7 Participants | 12 Participants | 13 Participants | 5 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 15 |
| other Total, other adverse events | 7 / 18 | 7 / 18 | 8 / 18 | 8 / 15 |
| serious Total, serious adverse events | 1 / 18 | 2 / 18 | 4 / 18 | 1 / 15 |
Outcome results
Primary
Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
This study is descriptive and no primary or secondary efficacy endpoints are defined.
Time frame: 5 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CTAP101 | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 2 Moderate | 1 number of TEAE count |
| CTAP101 | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 1 Mild | 39 number of TEAE count |
| CTAP101 | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 5 Fatal | 0 number of TEAE count |
| CTAP101 | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 3 Severe | 2 number of TEAE count |
| CTAP101 | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade Potentially Life Threatening | 0 number of TEAE count |
| Immediate-release (IR) Calcifediol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 3 Severe | 3 number of TEAE count |
| Immediate-release (IR) Calcifediol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade Potentially Life Threatening | 0 number of TEAE count |
| Immediate-release (IR) Calcifediol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 5 Fatal | 0 number of TEAE count |
| Immediate-release (IR) Calcifediol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 2 Moderate | 3 number of TEAE count |
| Immediate-release (IR) Calcifediol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 1 Mild | 12 number of TEAE count |
| Cholecalciferol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 2 Moderate | 8 number of TEAE count |
| Cholecalciferol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 1 Mild | 13 number of TEAE count |
| Cholecalciferol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 3 Severe | 0 number of TEAE count |
| Cholecalciferol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade Potentially Life Threatening | 0 number of TEAE count |
| Cholecalciferol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 5 Fatal | 0 number of TEAE count |
| Paricalcitol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade Potentially Life Threatening | 0 number of TEAE count |
| Paricalcitol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 2 Moderate | 5 number of TEAE count |
| Paricalcitol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 1 Mild | 10 number of TEAE count |
| Paricalcitol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 3 Severe | 1 number of TEAE count |
| Paricalcitol | Incidence and Severity of Treatment-Emergent Adverse Events (TEAE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. | Grade 5 Fatal | 0 number of TEAE count |