Safety, Tolerability, and Clinical Effects of Twice-daily Doses of Cinacalcet (AMG 073) in Adults With Primary Hyperparathyroidism (HPT)
Primary Purpose
Primary Hyperparathyroidism
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Cinacalcet
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Primary Hyperparathyroidism
Eligibility Criteria
Inclusion Criteria:
- Men or women ≥ 18 years old before beginning of screening
- Use, in the opinion of the principal investigator, effective contraceptive measures throughout the study
- Negative serum pregnancy test within 15 days before day 0
- Plasma iPTH concentration > 45 pg/mL on at least 2 occasions (during the screening phase) at least 7 days apart
- Serum calcium concentration ≥ 11 mg/dL on 2 occasions (during the screening phase) at least 7 days apart
- 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 transaminase (AST), alanine transaminase (ALT), and total bilirubin ≤ 2 times the upper limit of normal (central laboratory's range)
- Laboratory test results within the central laboratory's normal range for hematology, coagulation, urinalysis, and clinical chemistry parameters not mentioned specifically in other inclusion/exclusion criteria
- Chest x-ray within the past 12 months, with no evidence of an active infectious, inflammatory, or malignant process
- Informed consent for participation in the study
Exclusion Criteria:
- Any unstable medical condition requiring hospitalization within 30 days before day 0, or otherwise unstable condition in the judgment of the investigator
- Awaiting or scheduled for parathyroidectomy within 2 months after study day 0
- Pregnant or nursing
- Received, within 21 days before day 0, therapy with systemic glucocorticoids (> 5 mg/day prednisone or equivalent), lithium, tricyclic antidepressants (with the exception of amitriptyline and nortriptyline), thioridazine, haloperidol, flecainide, drugs with a narrow therapeutic index that are primarily metabolized by hepatic cytochrome P450 CYP 2D6, drugs that affect renal tubular calcium handling (ie, thiazide or loop diuretics), or calcitonin
- Dose changes in bisphosphonates, thyroid replacement therapy, selective estrogen receptor modulators (SERMs), or changes in daily doses of estrogen (greater than 0.75 mg) within 90 days before day 0
- Subjects who discontinued estrogen or SERM therapy must have been off treatment for at least 90 days before day 0.
- Alcohol or illicit drug abuse within 12 months before day 0 based on self-report
- Myocardial infarction within 6 months before day 0
- Ventricular rhythm disturbance requiring current treatment
- Seizure within 12 months before day 0
- History (within 5 years) of malignancy of any type, other than nonmelanomatous skin cancers or in situ cervical cancer
- Evidence (within 5 years) of treatment for and/or active sarcoidosis, tuberculosis, or diseases other than primary HPT known to cause hypercalcemia
- History of familial hypocalciuric hypercalcemia (FHH)
- Uncontrolled diabetes, as defined by hemoglobin A1c (HbA1c) ≥ 8.0
- Gastrointestinal disorder that may be associated with impaired absorption of orally administered medications
- Inability to swallow tablets similar in size to an aspirin tablet
- Known sensitivity to products administered during the study
- Previous participation as a subject in this study (ie, withdrawn early) or a prior study involving AMG 073 administration
- Enrolled in, or not yet completed at least 28 days since ending other investigational device or drug trial(s)
- Psychiatric disorder that would interfere with understanding and giving informed consent or compliance with protocol requirements
- Any other condition that might reduce the chance of obtaining data (ie, known poor compliance) required by the protocol or that might compromise the ability to give truly informed consent
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Cinacalcet
Placebo
Arm Description
Participants received 65 mg cinacalcet orally twice a day for 4 weeks.
Participants received placebo to cinacalcet orally twice a day for 4 weeks.
Outcomes
Primary Outcome Measures
Number of Participants with Adverse Events
Number of Participants with Clinically Significant Laboratory Tests, Vital Signs or Electrocardiogram Assessments
Secondary Outcome Measures
Percent Change from Baseline in Serum Calcium
Percent Change from Baseline in Plasma Intact Parathyroid Hormone (iPTH)
Percent Change from Baseline in Bone-specific Alkaline Phosphatase (BALP)
Percent Change from Baseline in 1,25 dihydroxy Vitamin D3
Percent Change from Baseline in Serum Phosphorus
Percent Change from Baseline in N-telopeptide (NTx)
Percent Change from Baseline in Urine Osmolality
Percent Change from Baseline in Calcium/Creatinine Ratio
Percent Change from Baseline in Phosphorus/Creatinine Ratio
Percent Change from Baseline in N-telopeptide/Creatinine Ratio
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03776058
Brief Title
Safety, Tolerability, and Clinical Effects of Twice-daily Doses of Cinacalcet (AMG 073) in Adults With Primary Hyperparathyroidism (HPT)
Official Title
A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Safety, Tolerability, and Clinical Effects of Twice-daily Doses of an Oral Calcimimetic Agent (AMG 073) in Subjects With Primary Hyperparathyroidism (HPT)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
June 15, 2000 (Actual)
Primary Completion Date
December 26, 2000 (Actual)
Study Completion Date
December 26, 2000 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objectives were to assess the safety and tolerability of twice daily (BID) doses of 65 mg cinacalcet administered orally to adults with primary HPT.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Hyperparathyroidism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cinacalcet
Arm Type
Experimental
Arm Description
Participants received 65 mg cinacalcet orally twice a day for 4 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo to cinacalcet orally twice a day for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Cinacalcet
Other Intervention Name(s)
AMG 073, Sensipar®, Mimpara®
Intervention Description
Tablets for oral administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablets for oral administration
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events
Time Frame
4 weeks
Title
Number of Participants with Clinically Significant Laboratory Tests, Vital Signs or Electrocardiogram Assessments
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Percent Change from Baseline in Serum Calcium
Time Frame
Baseline and week 4
Title
Percent Change from Baseline in Plasma Intact Parathyroid Hormone (iPTH)
Time Frame
Baseline and week 4
Title
Percent Change from Baseline in Bone-specific Alkaline Phosphatase (BALP)
Time Frame
Baseline and week 4
Title
Percent Change from Baseline in 1,25 dihydroxy Vitamin D3
Time Frame
Baseline and week 4
Title
Percent Change from Baseline in Serum Phosphorus
Time Frame
Baseline and week 4
Title
Percent Change from Baseline in N-telopeptide (NTx)
Time Frame
Baseline and week 4
Title
Percent Change from Baseline in Urine Osmolality
Time Frame
Baseline and week 4
Title
Percent Change from Baseline in Calcium/Creatinine Ratio
Time Frame
Baseline and week 4
Title
Percent Change from Baseline in Phosphorus/Creatinine Ratio
Time Frame
Baseline and week 4
Title
Percent Change from Baseline in N-telopeptide/Creatinine Ratio
Time Frame
Baseline and week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men or women ≥ 18 years old before beginning of screening
Use, in the opinion of the principal investigator, effective contraceptive measures throughout the study
Negative serum pregnancy test within 15 days before day 0
Plasma iPTH concentration > 45 pg/mL on at least 2 occasions (during the screening phase) at least 7 days apart
Serum calcium concentration ≥ 11 mg/dL on 2 occasions (during the screening phase) at least 7 days apart
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 transaminase (AST), alanine transaminase (ALT), and total bilirubin ≤ 2 times the upper limit of normal (central laboratory's range)
Laboratory test results within the central laboratory's normal range for hematology, coagulation, urinalysis, and clinical chemistry parameters not mentioned specifically in other inclusion/exclusion criteria
Chest x-ray within the past 12 months, with no evidence of an active infectious, inflammatory, or malignant process
Informed consent for participation in the study
Exclusion Criteria:
Any unstable medical condition requiring hospitalization within 30 days before day 0, or otherwise unstable condition in the judgment of the investigator
Awaiting or scheduled for parathyroidectomy within 2 months after study day 0
Pregnant or nursing
Received, within 21 days before day 0, therapy with systemic glucocorticoids (> 5 mg/day prednisone or equivalent), lithium, tricyclic antidepressants (with the exception of amitriptyline and nortriptyline), thioridazine, haloperidol, flecainide, drugs with a narrow therapeutic index that are primarily metabolized by hepatic cytochrome P450 CYP 2D6, drugs that affect renal tubular calcium handling (ie, thiazide or loop diuretics), or calcitonin
Dose changes in bisphosphonates, thyroid replacement therapy, selective estrogen receptor modulators (SERMs), or changes in daily doses of estrogen (greater than 0.75 mg) within 90 days before day 0
Subjects who discontinued estrogen or SERM therapy must have been off treatment for at least 90 days before day 0.
Alcohol or illicit drug abuse within 12 months before day 0 based on self-report
Myocardial infarction within 6 months before day 0
Ventricular rhythm disturbance requiring current treatment
Seizure within 12 months before day 0
History (within 5 years) of malignancy of any type, other than nonmelanomatous skin cancers or in situ cervical cancer
Evidence (within 5 years) of treatment for and/or active sarcoidosis, tuberculosis, or diseases other than primary HPT known to cause hypercalcemia
History of familial hypocalciuric hypercalcemia (FHH)
Uncontrolled diabetes, as defined by hemoglobin A1c (HbA1c) ≥ 8.0
Gastrointestinal disorder that may be associated with impaired absorption of orally administered medications
Inability to swallow tablets similar in size to an aspirin tablet
Known sensitivity to products administered during the study
Previous participation as a subject in this study (ie, withdrawn early) or a prior study involving AMG 073 administration
Enrolled in, or not yet completed at least 28 days since ending other investigational device or drug trial(s)
Psychiatric disorder that would interfere with understanding and giving informed consent or compliance with protocol requirements
Any other condition that might reduce the chance of obtaining data (ie, known poor compliance) required by the protocol or that might compromise the ability to give truly informed consent
12. IPD Sharing Statement
Learn more about this trial
Safety, Tolerability, and Clinical Effects of Twice-daily Doses of Cinacalcet (AMG 073) in Adults With Primary Hyperparathyroidism (HPT)
We'll reach out to this number within 24 hrs