Evaluation of the Effectiveness of Paricalcitol Versus Cinacalcet With Low-Dose Vitamin D (IMPACT SHPT)

Abbott

Status and phase: Completed; Phase 4

Conditions: Chronic Kidney Disease; Hemodialysis; Secondary Hyperparathyroidism

Treatments: Drug: Cinacalcet; Drug: Paricalcitol

Study type: Interventional

Funder types: Industry

Identifiers

NCT00977080

2009-011378-14 (EudraCT Number)

M10-967

Details and patient eligibility

About

Evaluates the effectiveness of on-label Paricalcitol versus Cinacalcet with Low-Dose Vitamin D.

Full description

During a 4-week washout period, participants stopped taking cinacalcet or other vitamin D receptor activators (VDRAs). (Participants who were naive to cinacalcet or VDRAs did not have to wash out). At randomization, participants entered a 28-week open-label treatment period, during which they received either cinacalcet or paricalcitol. Participants who were assigned to receive paricalcitol were dosed according to the approved label in their respective geographic regions (i.e., IV at sites in the US and Russia and oral at sites in Europe). Supplemental cinacalcet was administered to participants in the paricalcitol arms who developed hypercalcemia (defined as >= 10.5 mg/dL). The evaluation period was from Weeks 21 to 28.

Enrollment: 272 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Male or female patients >= 18 years old.

2. Patient was diagnosed with Stage 5 chronic kidney disease (CKD) and had been receiving intravenous (IV) or oral vitamin D receptor activators (VDRAs) or cinacalcet during the 8 weeks prior to the screening period or naïve patients who had not received VDRA or cinacalcet within 8 weeks of screening.

3. Patient was on maintenance HD (hemodialysis) 3 times weekly (TIW) for at least 3 months prior to screening and was expected to remain on HD for the duration of the study.

4. For entry into the Pre-Treatment Washout Period (for patients who were not naïve to VDRAs and cinacalcet), the patient had to have screening laboratory values of:

   • iPTH level 130 to 700 pg/mL
   • Serum Total Alkaline Phosphatase level >= 40 U/L
   • Calcium level <= 10.0 mg/dL (2.49 mmol/L)
   • Calcium-phosphorus product (CaxP) <= 75 mg2/dL2 (US) and <= 70 mg2/dL2 (non-US)

Exclusion Criteria

1. Patient had a history of parathyroidectomy.
2. Patient had a current malignancy (with the exception of basal or squamous cell carcinoma of the skin), or clinically significant liver disease, in the opinion of the investigator.
3. Use of known inhibitors (i.e., ketoconazole) or inducers (i.e., carbamazepine) of cytochrome P450 (including grapefruit and/or grapefruit juice) 3A (CYP3A) or drugs metabolized by cytochrome P450 2D6 (CYP2D6) (e.g., flecainide, vinblastine, thioridazine, and most tricyclic antidepressants) within 2 weeks prior to study drug administration. Commonly used beta blockers such as metoprolol and carvedilol are allowed but are metabolized by CYP2D6; thus, an adjustment to a lower dose may have been required.
4. Patient was known to be human immunodeficiency (HIV) positive.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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272 participants in 4 patient groups

IV Paricalcitol

Active Comparator group

Description:

Participants in the IV stratum received intravenous (IV) paricalcitol and, if hypercalcemia (calcium \>= 10.5 mg/dL), received 30 mg of oral cinacalcet. Paricalcitol was dosed at 0.07 mcg/kg with titration every 2 weeks.

Treatment:

Drug: Paricalcitol

Cinacalcet (at sites with IV paricalcitol)

Active Comparator group

Description:

Participants in the IV stratum received 30 mg of oral cinacalcet daily with a low-dose vitamin D receptor activator (VDRA) (doxercalciferol IV 1 mcg 3 times weekly (TIW) at sites in the US and alfacalcidol capsules 0.25 mcg daily at sites in Russia).

Treatment:

Drug: Cinacalcet

Oral paricalcitol

Active Comparator group

Description:

Participants in the oral stratum received oral paricalcitol and, if hypercalcemia (calcium \>= 10.5 mg/dL), received 30 mg of oral cinacalcet. Paricalcitol was dosed at mcg = IPTH/60 3 times weekly (TIW) with titration every 2 weeks.

Treatment:

Drug: Paricalcitol

Cinacalcet (at sites with oral paricalcitol)

Active Comparator group

Description:

Participants in the oral stratum received 30 mg of oral cinacalcet daily with a low-dose vitamin D receptor activator (VDRA) (alfacalcidol capsules 0.25 mcg daily).

Treatment:

Drug: Cinacalcet