A Phase 1 Study to Evaluate PK, Safety and Tolerability of AMG 416

NCT03283098 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 20140197
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 5

Brief Summary

This was a multiple-dose, double-blind, randomized, placebo-controlled study. Chinese subjects residing in Mainland China with chronic kidney disease (CKD) receiving hemodialysis were randomized in a 3:1 ratio to receive 5 mg intravenous (IV) of etelcalcetide or placebo 3 times a week (TIW) for approximately 4 weeks, with a subsequent follow up period of approximately 4 weeks. Doses were given at the end of each scheduled hemodialysis session on study days 1 through day 27 and subject participation was complete after day 55 end-of-study (EOS) procedures were performed. Doses were administered TIW for 4 weeks, for a total of 12 doses.

Conditions

Secondary Hyperparathyroidism

Keywords

Secondary hyperparathyroidism; Chronic kidney disease CKD; Intact parathyroid hormone iPTH; Hemodialysis

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27

  Tmax is the time to maximum drug concentration of plasma etelcalcetide after dosing on Days 1 and 27.

  Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration

• PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27

  Cmax was defined as the maximum observed plasma drug concentration measured between the time of drug administration to the beginning of the next dialysis session.

  Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration

• Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27

  AUClast was specifically defined in this study as the area under the concentration time curve measured from the time of drug administration to the beginning of the next dialysis session, following the first and last dose.

  Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29

• Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27

  Accumulation ratio, calculated as AUClast day 27/AUClast day 1.

  Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29

Secondary Outcomes (12)

• Participants With Treatment-Emergent Adverse Events (TEAEs)

  Day 1 up to Day 55 (end of study)

• Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest

  Day 1 up to Day 55 (end of study)

• Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study

  Baseline is Day -2; End of Study is Day 55

• Change From Baseline to End of Study in Weight

  Day 1 up to Day 55

• Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures

  Baseline Day 1 prior to dialysis; End of Study is Day 55

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Intravenous (IV) administration of placebo three times a week (TIW) for 4 weeks for a total of 12 doses. Participants were followed for an additional 4 weeks.

Drug: Placebo

Etelcalcetide

EXPERIMENTAL

5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) for 4 weeks for a total of 12 doses. Participants were followed for an additional 4 weeks.

Drug: Etelcalcetide

Interventions

Etelcalcetide DRUG

Etelcalcetide was supplied as a sterile, preservative-free, aqueous solution in a single-use 3 mL glass vial.

Also known as: AMG 416

Etelcalcetide

Placebo DRUG

Placebo supplied to match active intervention.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures
• Resident in Mainland China and of Chinese ancestry
• Male or female subject ≥ 18 and ≤ 70 years of age at the time of screening, with end stage renal disease receiving hemodialysis
• Subject must be receiving hemodialysis 3 times weekly for at least 3 months through a functioning permanent dialysis access prior to Day -2 and have adequate hemodialysis with a delivered Kt/V ≥ 1.2 or urea reduction ratio (URR) ≥ 65% within 4 weeks to screening. The subject's routine hemodialysis session must be of 3-4.5 hours in duration, inclusive
• Subject has stable dialysis prescription and this prescription is not anticipated to significantly change during the course of the study

You may not qualify if:

• Corrected calcium (calculated) level is \< 2.07 mmol/L (8.3 mg/dL), and/or intact PTH level is outside the range of 31.8 - 127.3 pmol/L (300 - 1200 pg/mL)
• Female subjects who are pregnant, lactating/breastfeeding, or who plan to conceive, or breastfeed while on study through 3 months after receiving the dose of study drug
• Female subject of reproductive potential not willing to use a(n) acceptable method(s) of effective birth control during treatment with AMG 416, and for an additional 3 months after the end of treatment with AMG 416. Female subjects who have had a hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal ligation, or who are postmenopausal are not required to use contraception. Postmenopausal is defined as:
• Age \> 55 years with cessation of menses for 12 months or more
• Age \< 55 but no spontaneous menses for at least 2 years
• Age \< 55 years and spontaneous menses within the past 1 years, but currently amenorrheic, AND with postmenopausal gonadrotropin levels (luteinizing hormone and follicle-stimulating hormone levels \> 40 IU/L) or postmenopausal estradiol levels (\<5.3 pmol/L or 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved
• Underwent a bilateral oophorectomy
• Females of reproductive potential with a positive pregnancy test, unless medical follow-up confirms the subject is not pregnant
• Previous administration of AMG 416
• Subject has received cinacalcet within the 30 days prior to informed consent (treatment with cinacalcet is prohibited during the study)
• Subject has lost 500 mL or more of blood or plasma within 8 weeks of study drug administration or during the study period
• Anticipated or scheduled to have major surgical procedures during the study period such as kidney transplant or parathyroidectomy
• History of malignancy within 5 years before Day -2 (except non melanoma skin cancers, or cervical carcinoma in situ)
• Subject's 12-lead electrocardiogram (ECG) at screening suggests unstable arrhythmia or other cardiac abnormality that could place the subject at increased risk, based upon the Investigator's opinion
• Subject has current or history of cardiovascular conditions such as uncontrolled hypertension, symptomatic ventricular dysrhythmias, Torsades de Pointes, angina pectoris congestive heart failure (New York Heart Association Classification III or IV), myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 6 months prior to screening

Sponsors & Collaborators

• Amgen: lead

Study Sites (5)

Research Site

Beijing, Beijing Municipality, 100044, China

Location

Research Site

Nanjing, Jiangsu, 210029, China

Location

Research Site

Shanghai, Shanghai Municipality, 200032, China

Location

Research Site

Shanghai, Shanghai Municipality, 200040, China

Location

Research Site

Shanghai, Shanghai Municipality, 200127, China

Location

Related Publications (1)

• Xing C, Chen J, Zuo L, Fang Y, Ding X, Ni Z, Kong C, Shi G, Lu H, Hellawell J, Cheng S, Sohn W. A Phase I, Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Etelcalcetide Administered Intravenously to Chinese Patients With Chronic Kidney Disease Undergoing Hemodialysis. Clin Ther. 2021 Nov;43(11):2013-2023. doi: 10.1016/j.clinthera.2021.09.019. Epub 2021 Nov 11.

  PMID: 34774334 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperparathyroidism, Secondary; Renal Insufficiency, Chronic

Interventions

etelcalcetide hydrochloride

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multiple dose, double-blind, randomized, placebo-controlled clinical study conducted in Chinese subjects residing in Mainland China with chronic kidney disease receiving hemodialysis. The treatment duration will be approximately 4 weeks with a post treatment followup of 4 weeks. A dose will be given at each scheduled hemodialysis session (Dose administered three times a week for 4 weeks, for a total of 12 doses).

Study Record Dates

• First Submitted: August 31, 2017
• First Posted: September 14, 2017
• Study Start: March 1, 2018
• Primary Completion: February 4, 2019
• Study Completion: February 4, 2019
• Last Updated: February 10, 2020
• Results First Posted: February 10, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

CN (5)