Head-to-Head Study of Etelcalcetide (AMG 416) and Cinacalcet

Phase 3

Completed

Conditions: Secondary Hyperparathyroidism
Chronic Kidney Disease

Interventions: Drug: Cinacalcet
Drug: Etelcalcetide
Drug: Intravenous Placebo
Drug: Oral Placebo

Registration Number: NCT01896232

Lead Sponsor: Amgen

Brief Summary: The purpose of this study is to demonstrate that treatment with etelcalcetide (AMG 416) is not inferior to treatment with cinacalcet for lowering serum parathyroid hormone (PTH) levels by \> 30% from baseline among patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) who require management with hemodialysis.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 683

Inclusion Criteria

Eligible subjects must be receiving adequate thrice weekly maintenance hemodialysis with a dialysate calcium concentration ≥ 2.5 mEq/L for at least 3 months prior to screening laboratory assessments
Subjects must have SHPT as defined by one central laboratory screening predialysis serum PTH value > 500 pg/mL, measured on separate days within 2 weeks prior to randomization
Subjects must have one serum cCa value ≥ 8.3 mg/dL obtained before dialysis within 2 weeks of the date of randomization
Subjects receiving calcium supplements must have no more than a maximum dose change of 50% within 2 weeks before screening laboratory assessments are obtained, and the dose must remain unchanged through randomization

Exclusion Criteria

Eligible subjects cannot have received cinacalcet during the 3 months preceding the first screening laboratory assessment
Other criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cinacalcet	Intravenous Placebo	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 30 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining corrected calcium (cCa) ≥ 8.3 mg/dL.
Etelcalcetide	Oral Placebo	Participants were randomized to receive etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW, and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.
Cinacalcet	Cinacalcet	Participants were randomized to receive oral cinacalcet once daily and placebo intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 30 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining corrected calcium (cCa) ≥ 8.3 mg/dL.
Etelcalcetide	Etelcalcetide	Participants were randomized to receive etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW, and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With > 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis	Baseline and the efficacy assessment phase (EAP; defined as Weeks 20 to 27, inclusive).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With > 50% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase	Baseline and the efficacy assessment phase (Weeks 20 to 27, inclusive).
Percentage of Participants With > 30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase	Baseline and the efficacy assessment phase (Week 20 to Week 27)
Mean Number of Days of Vomiting or Nausea Per Week in the First 8 Weeks	First 8 weeks	Participants completed the Nausea/Vomiting Symptom Assessment (NVSA) questionnaire daily. This questionnaire asked participants to indicate the severity of nausea on a scale from 0 (no nausea) to 10 (as severe as can be imagined) and if they had vomited in the past 24 hours. A day of vomiting or nausea was defined as those where the severity of nausea score was \> 0 or where the episodes of vomiting score was \> 0.
Percent Change From Baseline in Mean Corrected Calcium During the Efficacy Assessment Phase	Baseline and the efficacy assessment phase (weeks 20 - 27)
Percentage of Participants With Mean Predialysis Serum Phosphorus ≤ 4.5 mg/dL During the Efficacy Assessment Phase	Efficacy assessment phase (weeks 20 - 27)
Mean Severity of Nausea in the First 8 Weeks	First 8 weeks	Severity of nausea was assessed using the Nausea and Vomiting Symptom Assessment questionnaire which asked participants to rate the severity of nausea on a scale from 0 (no nausea) to 10 (as severe as can be imagined). For each participant, the mean severity of nausea was calculated by averaging all available daily severities (including zeroes) reported in the first 8 weeks.
Mean Number of Episodes of Vomiting Per Week in the First 8 Weeks	First 8 weeks	The number of vomiting episodes was assessed using the Nausea and Vomiting Symptom Assessment questionnaire which asks participants on a daily basis how many times they vomited in the past 24 hours. The number of episodes in a week is the sum of all reported daily episodes in the week. For participants providing less than 7 days of responses to NVSA questions in any given week, data from that week did not contribute to the analysis.