Study to Evaluate Cinacalcet in Children With Chronic Kidney Disease

NCT01290029 | Completed Phase 1 Results

• 1 other identifier: 20090005
• Study Type: interventional
• Target: 14
• Locations: 3 countries
• Sites: 10

Brief Summary

The primary objective of the study was to evaluate the safety and tolerability of cinacalcet after a single oral dose in children aged 28 days to less than 6 years with chronic kidney disease receiving dialysis.

Conditions

Chronic Kidney Disease; Hyperparathyroidism, Secondary; Secondary Hyperparathyroidism

Keywords

pediatric; CKD; dialysis; paediatric

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: • fatal • life threatening • requires in patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other medically important serious event. Treatment-related adverse events are those the investigator assessed as being possibly related to any study mandated activity (eg, administration of investigational product, protocol-required therapies, device(s) and/or procedure). Events of interest included acute pancreatitis, convulsions, drug related hepatic disorders, fractures, hypersensitivity, hypocalcemia, ischaemic heart disease, ventricular tachyarrhythmias, cardiac failure, and hypotension.

  Day 1 to day 30

Secondary Outcomes (9)

• Area Under the Plasma Concentration Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) for Cinacalcet

  Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

• Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf) for Cinacalcet

  Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

• Maximum Observed Plasma Concentration (Cmax) of Cinacalcet

  Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

• Time to Reach Maximum Observed Plasma Concentration of Cinacalcet (Tmax)

  Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

• Terminal Half-life of Cinacalcet

  Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose

Study Arms (1)

Cinacalcet

EXPERIMENTAL

Participants received a single, oral dose of 0.25 mg/kg cinacalcet.

Drug: Cinacalcet

Interventions

Cinacalcet DRUG

Single, oral dose of 0.25 mg/kg cinacalcet

Also known as: Sensipar®, Mimpara®

Cinacalcet

Eligibility Criteria

• Age: 28 Days - 2190 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject's parent, or legally acceptable guardian, must sign an Independent Ethics Committee (IEC) or Institutional Review Board (IRB) approved Informed Consent Form.
• Subjects 28 days to \< 6 years of age with chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT) as diagnosed by principal investigators, undergoing hemodialysis or peritoneal dialysis at the time of screening (subjects 6 months or older should have been receiving dialysis for ≥ 1 months) and who have not received any cinacalcet HCl therapy for at least 2 weeks prior to dosing on Day 1
• Free of any disease or condition (other than those diseases or conditions related to their renal disease that, in the opinion of the investigator, would impact the subject's safety or the integrity of the study data).
• Must weigh ≥ 6 kg at screening and at Day-1.
• Must be at least 30 weeks of gestational age.
• Physical examination must be acceptable to the investigator at screening and at Day -1.
• Hemoglobin ≥ 8 g/dL at screening and at Day -1.
• Serum calcium within age-appropriate normal ranges per the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines at screening and at Day -1
• Normal or clinically acceptable electrocardiogram (ECG) (12-lead reporting RR, PR, QRS, and QTc intervals) at screening and at Day -1.
• Clinical laboratory tests that are acceptable to the investigator at screening and at Day -1.

You may not qualify if:

• Current or historic malignancy.
• Cardiac ventricular arrhythmias within 28 days prior to screening.
• A gastrointestinal disorder or surgery that could affect the absorption of drugs (eg, pyloric stenosis or any gut-shortening surgical procedure prior to screening).
• A new onset of seizure or worsening of a pre-existing seizure disorder within 2 months prior to IP administration.
• Major surgery (defined as any surgical procedure that involves general anesthesia or respiratory assistance) within 28 days prior to screening.
• Hepatic impairment indicated by elevated levels of hepatic transaminase or bilirubin (aspartate aminotransferase (AST) ≥ 1.5 x upper limit of normal (ULN) OR alanine aminotransferase (ALT) ≥ 1.5 x ULN OR total bilirubin ≥ 1 x ULN per institutional laboratory range) at screening or Day-1.
• History of prolongation of the QT interval (eg, congenital long QT interval, second or third degree heart block or other conditions which prolong the QT interval)
• Corrected QT Interval (QTc) \> 500 ms during screening, using Bazett's formula
• QTc ≥ 450 and ≤ 500 ms during screening, using Bazett's formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist
• Known hypersensitivity to cinacalcet HCl or any of the excipients in cinacalcet HCl.
• Use of grapefruit juice, herbal medications or potent CYP 3A4 inhibitors (eg, erythromycin, clarithromycin, ketokonazole, itraconazole) within the 14 days prior to enrollment and during the study.
• Concurrent or within 28 days prior to enrollment use of medications that are predominantly metabolized by the enzyme CYP2D6 and have a narrow therapeutic index (eg, flecainide, vinblastine, thioridazine, tricyclic antidepressants such as desipramine and imipramine, and beta-blockers such as metoprolol or carvedilol).
• Concurrent or within 28 days prior to enrollment use of medications that prolong QT interval (eg, sotalol, amiodarone, erythromycin, or clarithromycin).
• Currently receiving treatment in another investigational device or drug study, or less than 90 days since ending treatment on another investigational device or drug study(s).
• Other investigational procedures while participating in this study are excluded.

Sponsors & Collaborators

• Amgen: lead

Study Sites (10)

Research Site

Los Angeles, California, 90095, United States

Location

Research Site

San Francisco, California, 94143, United States

Location

Research Site

Louisville, Kentucky, 40202, United States

Location

Research Site

Kansas City, Missouri, 64108, United States

Location

Research Site

Heidelberg, 69120, Germany

Location

Research Site

Bristol, BS2 8BJ, United Kingdom

Location

Research Site

Glasgow, G3 8SJ, United Kingdom

Location

Research Site

Leeds, LS1 3EX, United Kingdom

Location

Research Site

Manchester, M13 9WL, United Kingdom

Location

Research Site

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (3)

• Chen P, Sohn W, Narayanan A, Gisleskog PO, Melhem M. Bridging adults and paediatrics with secondary hyperparathyroidism receiving haemodialysis: a pharmacokinetic-pharmacodynamic analysis of cinacalcet. Br J Clin Pharmacol. 2019 Jun;85(6):1312-1325. doi: 10.1111/bcp.13900. Epub 2019 Apr 25.

  PMID: 30756425 BACKGROUND

• Sohn WY, Portale AA, Salusky IB, Zhang H, Yan LL, Ertik B, Shahinfar S, Lee E, Dehmel B, Warady BA. An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis. Pediatr Nephrol. 2019 Jan;34(1):145-154. doi: 10.1007/s00467-018-4054-8. Epub 2018 Aug 23.

  PMID: 30141180 BACKGROUND

• Warady BA, Ng E, Bloss L, Mo M, Schaefer F, Bacchetta J. Cinacalcet studies in pediatric subjects with secondary hyperparathyroidism receiving dialysis. Pediatr Nephrol. 2020 Sep;35(9):1679-1697. doi: 10.1007/s00467-020-04516-4. Epub 2020 May 4.

  PMID: 32367309 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary

Interventions

Cinacalcet

Condition Hierarchy (Ancestors)

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; Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2011
• First Posted: February 4, 2011
• Study Start: January 25, 2011
• Primary Completion: September 23, 2015
• Study Completion: September 23, 2015
• Last Updated: June 17, 2020
• Results First Posted: December 19, 2016

Record last verified: 2020-06

Locations

DE (1); US (4); GB (5)