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

2018年12月11日 更新者:Amgen

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

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.

調査の概要

研究の種類

介入

入学 (実際)

48

段階

  • フェーズ2

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria:

  1. 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).

  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.
  3. 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.
  4. Acceptable renal function, with an estimated creatinine clearance > 50 ml/min as determined by the Cockroft and Gault equation.
  5. Acceptable hepatic function, defined as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin < 2 times the upper limit of normal.
  6. Fasting (8 hours) serum glucose ≤ 130 mg/dL and hemoglobin Alc within the central laboratory's normal range.
  7. Hematology panel, serum clinical chemistry and urinalysis results within normal ranges
  8. Chest x-ray without evidence of active, infectious, inflammatory or malignant process.

Exclusion Criteria:

  1. Any unstable medical condition, defined as having been hospitalized within 28 at prior to baseline, or otherwise unstable in the judgement of the investigator.
  2. 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])
  3. Received, within 90 days prior to Baseline, chronic therapy with bisphosphonates or fluoride.
  4. Known alcohol abuse, or use of illicit drugs, within 12 months prior to Baseline
  5. Experienced a myocardial infarction (MI) within 6 months prior to Baseline
  6. A ventricular rhythm disturbance requiring current treatment
  7. Received investigational drugs within 28 days prior to Baseline
  8. A history of seizures within 12 months prior to Baseline
  9. A history (within 5 years) of malignancy of any type, other than nonmelanomatous skin cancers or in situ cervical cancer
  10. A gastrointestinal disorder that may be associated with impaired absorption of orally administered medications
  11. A Body Mass Index (BMI) < 15 or > 40, obtained during screening
  12. An inability to swallow capsules
  13. Sarcoidosis, tuberculosis, or other diseases known to cause hypercalcemia
  14. Fasting spot urine calcium/creatinine ratio (mg) < 0.05
  15. A psychiatric disorder that would interfere with understanding and giving informed consent or compliance with protocol requirements
  16. 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.
  17. For Part 2, a subject from Part 1 who discontinued treatment early

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

  • 主な目的:処理
  • 割り当て:ランダム化
  • 介入モデル:順次割り当て
  • マスキング:ダブル

武器と介入

参加者グループ / アーム
介入・治療
プラセボコンパレーター:Placebo
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.
経口投与用カプセル
実験的:Cinacalcet 50 mg QD
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.
Capsule for oral administration
他の名前:
  • AMG 073
  • センシパー®
  • ミンパラ®
実験的:Cinacalcet 75 mg QD
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.
Capsule for oral administration
他の名前:
  • AMG 073
  • センシパー®
  • ミンパラ®
実験的:Cinacelcet 100 mg QD
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.
Capsule for oral administration
他の名前:
  • AMG 073
  • センシパー®
  • ミンパラ®

この研究は何を測定していますか?

主要な結果の測定

結果測定
時間枠
Number of Participants with Adverse Events in Part 1 and Part 2
時間枠:6 weeks in Part 1 and 15 days in Part 2
6 weeks in Part 1 and 15 days in Part 2

二次結果の測定

結果測定
メジャーの説明
時間枠
Percent Change from Baseline in Serum Calcium Concentration
時間枠:Baseline and days 8, 15, 16, 29, 43, and 50 in Part 1 and days 1, 8, 15, and 22 in Part 2.
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
時間枠:Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
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
時間枠:Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
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
時間枠:Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Minimum Serum Calcium Concentration in Part 2
時間枠:Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
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 24-hour Dosing Interval in Part 1
時間枠:Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
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 12-hour Dosing Interval in Part 2
時間枠:Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
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
時間枠:Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Cumulative Time Over the Day When Serum Calcium was ≤ 10.3 mg/dL In Part 2
時間枠:Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Percent Change from Baseline in Plasma Intact parathyroid Hormone (iPTH) Concentration
時間枠:Baseline and days 8, 15, 16, 29, 43, and 50 in Part 1 and days 1, 8, 15, and 22 in Part 2.
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 24 Hours After Dosing (AUC0-24) in Part 1
時間枠:Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Area Under the Plasma iPTH Concentration-time Curve from 0 to 12 Hours After Dosing (AUC0-12) in Part 2
時間枠:Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Minimum iPTH Concentration in Part 1
時間枠:Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Minimum iPTH Concentration in Part 2
時間枠:Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
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
時間枠:Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours postdose
Time of Minimum iPTH Concentration in Part 2
時間枠:Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
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 24-hour Dosing Interval in Part 1
時間枠:Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
Cumulative Time When iPTH was Below Baseline During the 12-hour Dosing Interval in Part 2
時間枠:Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
Cumulative Time iPTH was Below 45 pg/mL in Part 1
時間枠:Days 1, 8, and 43: Predose, 1, 2, 4, 8, 12, and 24 hours post dose
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
時間枠:Days 1 and 15: Predose, 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours postdose
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
時間枠:Baseline and days 8, 15, and 43 in Part 1
Baseline and days 8, 15, and 43 in Part 1
Percentage of Participants with Serum Calcitonin Concentration Less than 10 pg/mL
時間枠:Baseline and days 8, 15 and 43 in Part 1
Baseline and days 8, 15 and 43 in Part 1
Percent Change from Baseline in Bone-specific Alkaline Phosphatase (BALP) Concentration
時間枠:Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Percentage of Participants with BALP Concentration Within Normal Range
時間枠:Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Normal range of BALP is 2.9 to 20.1 ng/mL for men 20 to 79 years of age and and 3.7 to 20.9 ng/mL for women 20 to 79 years of age.
Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Percent Change from Baseline in Serum N-telopeptide (NTx) Concentration
時間枠:Baseline and days 8 and 15 in Part 1
Baseline and days 8 and 15 in Part 1
Percentage of Participants with Serum NTx Concentration Within Normal Range
時間枠:Baseline and days 8 and 15 in Part 1
Normal range of serum NTx is 5.4 to 24.2 nmoL bone collagen equivalents (BCE)/L for men, 6.2 to 19.0 nmoL BCE/L for premenopausal women, and 5.3 to 35.8 nmol BCE/L for postmenopausal women (≥ 55 years).
Baseline and days 8 and 15 in Part 1
Percent Change from Baseline in Urinary NTx Concentration
時間枠:Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Percentage of Participants with Urinary NTx Concentration Within Normal Range
時間枠:Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Normal range of urinary NTx is is 0.0 to 85.0 nmoL BCE/mmoL creatinine for men, 5.0 to 65.0 nmoL BCE/mmoL creatinine for premenopausal women, and 0.0 to 130.0 nmoL BCE/mmoL creatinine for postmenopausal women [≥ 55 years).
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
時間枠:Baseline and days 8 and 15 in Part 1
Baseline and days 8 and 15 in Part 1
Percent Change from Baseline in Urinary Calcium Concentration
時間枠:Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
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
時間枠:Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Normal range of urinary calcium is 50 to 300 mg/24 hours.
Baseline and days 15 and 43 in Part 1 and days 1, 8, and 15 in Part 2
Percent Change from Baseline in 1,25-Dihydroxy Vitamin D
時間枠:Baseline and days 8 and 43 in Part 1 and days 1 and 15 in part 2
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
時間枠:Baseline and days 8 and 43 in Part 1 and days 1 and 15 in part 2
The normal range for 1,25-dihydroxy vitamin D3 is 16.0 to 65.0 pg/mL.
Baseline and days 8 and 43 in Part 1 and days 1 and 15 in part 2
Percent Change from Baseline in Urinary and Serum Phosphorus Concentrations
時間枠:Baseline and days 8, 15, and 22 in Part 2
Baseline and days 8, 15, and 22 in Part 2

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

1998年9月29日

一次修了 (実際)

1999年12月13日

研究の完了 (実際)

1999年12月13日

試験登録日

最初に提出

2018年12月11日

QC基準を満たした最初の提出物

2018年12月11日

最初の投稿 (実際)

2018年12月13日

学習記録の更新

投稿された最後の更新 (実際)

2018年12月13日

QC基準を満たした最後の更新が送信されました

2018年12月11日

最終確認日

2018年12月1日

詳しくは

本研究に関する用語

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

はい

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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