Safety, Pharmacokinetics, and Clinical Effects of Cinacalcet (AMG 073) in Primary Hyperparathyroidism

NCT03774771 | Completed Phase 2 FDA Drug

• 1 other identifier: 00980125
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective was to assess the safety and tolerability of cinacalcet in adults with primary hyperparathyroidism (HPT) when administered as a single oral once daily doses for 6 consecutive weeks and twice daily for 15 consecutive days.

Conditions

Primary Hyperparathyroidism

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events in Part 1 and Part 2

  6 weeks in Part 1 and 15 days in Part 2

Secondary Outcomes (34)

• Percent Change from Baseline in Serum Calcium Concentration

  Baseline and days 8, 15, 16, 29, 43, and 50 in Part 1 and days 1, 8, 15, and 22 in Part 2.

• Area Under the Serum Calcium Concentration-time Curve from 0 to 24 Hours After Dosing (AUC0-24) in Part 1

  Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose

• Area Under the Serum Calcium Concentration-time Curve from 0 to 12 Hours After Dosing (AUC0-12) in Part 2

  Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose

• Minimum Serum Calcium Concentration in Part 1

  Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose

• Minimum Serum Calcium Concentration in Part 2

  Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose

Study Arms (4)

Placebo

PLACEBO COMPARATOR

In Part 1 participants received placebo capsules orally once a day for 6 weeks. In Part 2 participants received placebo capsules twice a day for 15 days.

Drug: Placebo

Cinacalcet 50 mg QD

EXPERIMENTAL

In Part 1 participants received 50 mg cinacalcet capsules orally once a day (QD) for 6 weeks. In Part 2 participants received 30 mg cinacalcet capsules twice a day for 15 days.

Drug: Cinacalcet

Cinacalcet 75 mg QD

EXPERIMENTAL

In Part 1 participants received 75 mg cinacalcet capsules orally once a day (QD) for 6 weeks. In Part 2 participants received 40 mg cinacalcet capsules twice a day for 15 days.

Drug: Cinacalcet

Cinacelcet 100 mg QD

EXPERIMENTAL

In Part 1 participants received 100 mg cinacalcet capsules orally once a day (QD) for 6 weeks. In Part 2 participants received 50 mg cinacalcet capsules twice a day for 15 days.

Drug: Cinacalcet

Interventions

Cinacalcet DRUG

Capsule for oral administration

Also known as: AMG 073, Sensipar®, Mimpara®

Cinacalcet 50 mg QD; Cinacalcet 75 mg QD; Cinacelcet 100 mg QD

Placebo DRUG

Capsules for oral administration

Placebo

Eligibility Criteria

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

You may qualify if:

• Males and females ≥ 18 years of age at screening. In Part 1, females must be postmenopausal (at least 12 months since last menstrual period) or surgically sterile.
• In Part 2, all qualified females replacing a Part 1 subject (i.e., naïve subjects), regardless of reproductive status, may participate if, in the opinion of the principal investigator, an appropriate effective contraceptive method is used throughout the study. All females must have a negative serum pregnancy test within 28 days prior to Baseline (Parts 1 and 2).
• Men and women participating in this study must agree to use, in the opinion of the principal investigator, highly effective contraceptive measures throughout the study. All females who are pregnant or breast-feeding are excluded. All subjects must notify the principal investigator if they or their partner suspects a pregnancy.
• Diagnosis of primary HPT. A plasma intact PTH concentration ≥ 45 pg/mL on at least two occasions at least 1 week apart during the 12 months prior to baseline (at least one of these determinations should be made during screening), and a corrected total serum calcium concentration (for each 1 g/dL decrease in albumin level below 4.0 g/dL, the calcium value should be increased by 0.8 mg/dL) greater than the upper limit of normal, but no greater than 12.5 mg/dL.
• Acceptable renal function, with an estimated creatinine clearance \> 50 ml/min as determined by the Cockroft and Gault equation.
• Acceptable hepatic function, defined as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin \< 2 times the upper limit of normal.
• Fasting (8 hours) serum glucose ≤ 130 mg/dL and hemoglobin Alc within the central laboratory's normal range.
• Hematology panel, serum clinical chemistry and urinalysis results within normal ranges
• Chest x-ray without evidence of active, infectious, inflammatory or malignant process.

You may not qualify if:

• Any unstable medical condition, defined as having been hospitalized within 28 at prior to baseline, or otherwise unstable in the judgement of the investigator.
• Received within 21 day prior to baseline, therapy with systemic glucocorticoids, lithium, tricyclic antidepressants, thioridazine, haloperidol, flecainide, or other drugs with a narrow therapeutic index that are primarily metabolized by hepatic cytochrome P450 CYP 2D6, drugs that affect renal tubular calcium handling (e.g. thiazide or loop diuretics), and drugs that affect bone metabolism (e.g. calcitonin, selective estrogen receptor modulators \[SERMs\])
• Received, within 90 days prior to Baseline, chronic therapy with bisphosphonates or fluoride.
• Known alcohol abuse, or use of illicit drugs, within 12 months prior to Baseline
• Experienced a myocardial infarction (MI) within 6 months prior to Baseline
• A ventricular rhythm disturbance requiring current treatment
• Received investigational drugs within 28 days prior to Baseline
• A history of seizures within 12 months prior to Baseline
• A history (within 5 years) of malignancy of any type, other than nonmelanomatous skin cancers or in situ cervical cancer
• A gastrointestinal disorder that may be associated with impaired absorption of orally administered medications
• A Body Mass Index (BMI) \< 15 or \> 40, obtained during screening
• An inability to swallow capsules
• Sarcoidosis, tuberculosis, or other diseases known to cause hypercalcemia
• Fasting spot urine calcium/creatinine ratio (mg) \< 0.05
• A psychiatric disorder that would interfere with understanding and giving informed consent or compliance with protocol requirements

Sponsors & Collaborators

• Amgen: lead

MeSH Terms

Conditions

Hyperparathyroidism, Primary

Interventions

Cinacalcet

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: December 13, 2018
• Study Start: September 29, 1998
• Primary Completion: December 13, 1999
• Study Completion: December 13, 1999
• Last Updated: December 13, 2018

Record last verified: 2018-12