NCT03774771已完成2 期
A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 6-week Dose-Ranging Study to Assess the Safety, Pharmacokinetics, and Clinical Effects of an Oral Calcimimetic Agent (AMG 073) in Primary Hyperparathyroidism
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 48
- 主要终点
- Number of Participants with Adverse Events in Part 1 and Part 2
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •Any other condition that might reduce the chance of obtaining data (eg, known poor compliance) required by the protocol or that might compromise the ability to give truly informed consent.
- •For Part 2, a subject from Part 1 who discontinued treatment early
研究组 & 干预措施
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.
干预措施: Placebo (Drug)
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.
干预措施: Cinacalcet (Drug)
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.
干预措施: Cinacalcet (Drug)
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.
干预措施: Cinacalcet (Drug)
结局指标
主要结局
Number of Participants with Adverse Events in Part 1 and Part 2
时间窗: 6 weeks in Part 1 and 15 days in Part 2
次要结局
- Minimum iPTH Concentration in Part 1(Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose)
- Cumulative Time When iPTH was Below Baseline During the 24-hour Dosing Interval in Part 1(Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose)
- Cumulative Time When Serum Calcium was Below Baseline During the 24-hour Dosing Interval in Part 1(Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose)
- Percent Change from Baseline in Plasma Intact parathyroid Hormone (iPTH) Concentration(Baseline and days 8, 15, 16, 29, 43, and 50 in Part 1 and days 1, 8, 15, and 22 in Part 2.)
- Time of Minimum iPTH Concentration in Part 2(Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose)
- Cumulative Time When iPTH was Below Baseline During the 12-hour Dosing Interval in Part 2(Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose)
- 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)
- Cumulative Time Over the Day When Serum Calcium was ≤ 10.3 mg/dL In Part 1(Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose)
- Minimum iPTH Concentration 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)
- Cumulative Time Over the Day When Serum Calcium was ≤ 10.3 mg/dL In Part 2(Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose)
- Percent Change from Baseline in Bone-specific Alkaline Phosphatase (BALP) Concentration(Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 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)
- 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)
- Cumulative Time When Serum Calcium was Below Baseline During the 12-hour Dosing Interval in Part 2(Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose)
- Area Under the Plasma iPTH 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)
- Cumulative Time iPTH was Below 45 pg/mL in Part 2(Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose)
- Percent Change from Baseline in Serum Calcitonin Concentration(Baseline and days 8, 15, and 43 in Part 1)
- Percent Change from Baseline in Serum N-telopeptide (NTx) Concentration(Baseline and days 8 and 15 in Part 1)
- Percent Change from Baseline in 1,25-Dihydroxy Vitamin D(Baseline and days 8 and 43 in Part 1 and days 1 and 15 in part 2)
- Percentage of Participants with 1,25-Dihydroxy Vitamin D Concentration in the Normal Range(Baseline and days 8 and 43 in Part 1 and days 1 and 15 in part 2)
- 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 Plasma iPTH 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)
- Time of Minimum iPTH Concentration in Part 1(Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose)
- Cumulative Time iPTH was Below 45 pg/mL in Part 1(Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose)
- Percentage of Participants with Urinary NTx Concentration Within Normal Range(Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2)
- Percentage of Participants with Serum Calcitonin Concentration Less than 10 pg/mL(Baseline and days 8, 15 and 43 in Part 1)
- Percentage of Participants with BALP Concentration Within Normal Range(Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2)
- Percentage of Participants with Serum NTx Concentration Within Normal Range(Baseline and days 8 and 15 in Part 1)
- Percent Change from Baseline in Urinary NTx Concentration(Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2)
- Percent Change from Baseline in Urinary Calcium/Creatinine Ratio(Baseline and days 8 and 15 in Part 1)
- Percent Change from Baseline in Urinary Calcium Concentration(Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2)
- Percentage of Participants with Urinary Calcium Concentration Within Normal Range(Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2)
- Percent Change from Baseline in Urinary and Serum Phosphorus Concentrations(Baseline and days 8, 15, and 22 in Part 2)
研究者
相似试验
已完成
1 期
Study to Evaluate Cinacalcet in Children With Chronic Kidney DiseaseHyperparathyroidism, SecondarySecondary HyperparathyroidismChronic Kidney DiseaseNCT01290029Amgen14
终止
3 期
Pediatric Chronic Kidney Disease Safety and EfficacyChronic Kidney DiseaseHyperparathyroidism, SecondarySecondary HyperparathyroidismKidney DiseaseHyperparathyroidismNCT01277510Amgen43
已完成
3 期
Cinacalcet HCl in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism Not Receiving DialysisChronic Kidney DiseaseKidney DiseaseNCT00094484Amgen400
已完成
3 期
Efficacy and Safety Study of Cinacalcet for the Treatment of Hypercalcemia in Patients With Primary Hyperparathyroidism Unable to Undergo ParathyroidectomyHyperparathyroidism, PrimaryHypercalcemiaNCT00975221Amgen67
终止
3 期
Efficacy and Safety of Cinacalcet in Pediatric Patients With Secondary Hyperparathyroidism (SHPT) and Chronic Kidney Disease (CKD) on DialysisChronic Kidney Disease, Secondary HyperparathyroidismNCT02138838Amgen55