A Phase 1 Study to Evaluate PK, Safety and Tolerability of AMG 416
A Phase 1, Multiple Dose, Randomized, Double-blind, Placebo-controlled Study to Evaluate Pharmacokinetics, Safety and Tolerability of AMG 416 Administered Intravenously to Chinese Subjects With Chronic Kidney Disease on Hemodialysis
This was a multiple-dose, double-blind, randomized, placebo-controlled study. Chinese subjects residing in Mainland China with chronic kidney disease (CKD) receiving hemodialysis were randomized in a 3:1 ratio to receive 5 mg intravenous (IV) of etelcalcetide or placebo 3 times a week (TIW) for approximately 4 weeks, with a subsequent follow up period of approximately 4 weeks.
Doses were given at the end of each scheduled hemodialysis session on study days 1 through day 27 and subject participation was complete after day 55 end-of-study (EOS) procedures were performed. Doses were administered TIW for 4 weeks, for a total of 12 doses.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
-
-
Beijing
-
Beijing、Beijing、中国、100044
- Research Site
-
-
Jiangsu
-
Nanjing、Jiangsu、中国、210029
- Research Site
-
-
Shanghai
-
Shanghai、Shanghai、中国、200032
- Research Site
-
Shanghai、Shanghai、中国、200127
- Research Site
-
Shanghai、Shanghai、中国、200040
- Research Site
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Subject has provided informed consent prior to initiation of any study-specific activities/procedures
- Resident in Mainland China and of Chinese ancestry
- Male or female subject ≥ 18 and ≤ 70 years of age at the time of screening, with end stage renal disease receiving hemodialysis
- Subject must be receiving hemodialysis 3 times weekly for at least 3 months through a functioning permanent dialysis access prior to Day -2 and have adequate hemodialysis with a delivered Kt/V ≥ 1.2 or urea reduction ratio (URR) ≥ 65% within 4 weeks to screening. The subject's routine hemodialysis session must be of 3-4.5 hours in duration, inclusive
- Subject has stable dialysis prescription and this prescription is not anticipated to significantly change during the course of the study
Exclusion Criteria:
- Corrected calcium (calculated) level is < 2.07 mmol/L (8.3 mg/dL), and/or intact PTH level is outside the range of 31.8 - 127.3 pmol/L (300 - 1200 pg/mL)
- Female subjects who are pregnant, lactating/breastfeeding, or who plan to conceive, or breastfeed while on study through 3 months after receiving the dose of study drug
Female subject of reproductive potential not willing to use a(n) acceptable method(s) of effective birth control during treatment with AMG 416, and for an additional 3 months after the end of treatment with AMG 416. Female subjects who have had a hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal ligation, or who are postmenopausal are not required to use contraception. Postmenopausal is defined as:
- Age > 55 years with cessation of menses for 12 months or more
- Age < 55 but no spontaneous menses for at least 2 years
- Age < 55 years and spontaneous menses within the past 1 years, but currently amenorrheic, AND with postmenopausal gonadrotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (<5.3 pmol/L or 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved
- Underwent a bilateral oophorectomy
- Females of reproductive potential with a positive pregnancy test, unless medical follow-up confirms the subject is not pregnant
- Previous administration of AMG 416
- Subject has received cinacalcet within the 30 days prior to informed consent (treatment with cinacalcet is prohibited during the study)
- Subject has lost 500 mL or more of blood or plasma within 8 weeks of study drug administration or during the study period
- Anticipated or scheduled to have major surgical procedures during the study period such as kidney transplant or parathyroidectomy
- History of malignancy within 5 years before Day -2 (except non melanoma skin cancers, or cervical carcinoma in situ)
- Subject's 12-lead electrocardiogram (ECG) at screening suggests unstable arrhythmia or other cardiac abnormality that could place the subject at increased risk, based upon the Investigator's opinion
- Subject has current or history of cardiovascular conditions such as uncontrolled hypertension, symptomatic ventricular dysrhythmias, Torsades de Pointes, angina pectoris congestive heart failure (New York Heart Association Classification III or IV), myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 6 months prior to screening
研究計画
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:並列代入
- マスキング:トリプル
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
Intravenous (IV) administration of placebo three times a week (TIW) for 4 weeks for a total of 12 doses.
Participants were followed for an additional 4 weeks.
|
Placebo supplied to match active intervention.
|
実験的:Etelcalcetide
5 mg intravenous (IV) dose of etelcalcetide three times a week (TIW) for 4 weeks for a total of 12 doses.
Participants were followed for an additional 4 weeks.
|
Etelcalcetide was supplied as a sterile, preservative-free, aqueous solution in a single-use 3 mL glass vial.
他の名前:
|
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 |
メジャーの説明 |
時間枠 |
---|---|---|
Pharmacokinetic (PK) Parameter: Time to Maximum Drug Concentration (Tmax) of Plasma Etelcalcetide on Days 1 and 27
時間枠:Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
|
Tmax is the time to maximum drug concentration of plasma etelcalcetide after dosing on Days 1 and 27.
|
Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
|
PK: Maximum Observed Drug Concentration (Cmax) of Plasma Etelcalcetide on Days 1 and 27
時間枠:Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
|
Cmax was defined as the maximum observed plasma drug concentration measured between the time of drug administration to the beginning of the next dialysis session.
|
Days 1 and 27; PK blood sampling predialysis, and at 10, 30, 60, 90 min postdose, as well as on Day 2 and 28 between 18 and 30 hours after study drug administration
|
Pharmacokinetic (PK) Parameter: Area Under the Curve From Time Zero to the Beginning of the Subsequent Hemodialysis Treatment (AUClast) of Plasma Etelcalcetide on Days 1 and 27
時間枠:Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
|
AUClast was specifically defined in this study as the area under the concentration time curve measured from the time of drug administration to the beginning of the next dialysis session, following the first and last dose.
|
Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
|
Pharmacokinetic (PK) Parameter: Accumulation Ratio Comparing Days 1 and 27
時間枠:Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
|
Accumulation ratio, calculated as AUClast day 27/AUClast day 1.
|
Days 1 and 27; PK blood sampling predialysis, and up to 44-50 hour postdose.at 10, 30, 60, 90 min postdose: Day 2 and 28 between 18 and 30 hours after study drug administration; Day 3 (predialysis) + Day 29
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Participants With Treatment-Emergent Adverse Events (TEAEs)
時間枠:Day 1 up to Day 55 (end of study)
|
The severity of each adverse event was assessed using the NCI-CTCAE Version 4.0 according to the following:
A serious AE is an AE that met one or more of the following criteria:
|
Day 1 up to Day 55 (end of study)
|
Participants With Treatment-Emergent Adverse Events (TEAEs) of Interest
時間枠:Day 1 up to Day 55 (end of study)
|
Terms were coded with Medical Dictionary for Regulatory Activities (MedDRA) version 21.1.
Narrow search criteria used for both standardized MedDRA queries (SMQ) and events of interest (EOI).
One preferred term (PT) could match multiple EOIs.
Infusion Reaction EOI counts included only those events which had onset day coinciding with study medication infusion and resolved on the same day or the day after onset.
|
Day 1 up to Day 55 (end of study)
|
Participants With Clinically-Significant Changes in Electrocardiograms (ECGs) From Baseline to End of Study
時間枠:Baseline is Day -2; End of Study is Day 55
|
Count of participants who exhibited a clinically significant change in the results of their 12-lead electrocardiograms (ECG) when comparing baseline to end of study ECGs.
|
Baseline is Day -2; End of Study is Day 55
|
Change From Baseline to End of Study in Weight
時間枠:Day 1 up to Day 55
|
Change from baseline in weight measured at visit.
|
Day 1 up to Day 55
|
Change From Baseline to End of Study in Systolic and Diastolic Blood Pressures
時間枠:Baseline Day 1 prior to dialysis; End of Study is Day 55
|
Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.
|
Baseline Day 1 prior to dialysis; End of Study is Day 55
|
Baseline and Change From Baseline to End of Study in Heart Rate
時間枠:Baseline Day 1 prior to dialysis; End of Study is Day 55
|
Participants remained seated for at least 10 minutes prior to measurement of predialysis heart rate and blood pressure.
|
Baseline Day 1 prior to dialysis; End of Study is Day 55
|
Change From Baseline to End of Study in Calcium
時間枠:Baseline is Day 1 prior to dialysis; End of Study is Day 55
|
Calcium was tested at a central laboratory.
|
Baseline is Day 1 prior to dialysis; End of Study is Day 55
|
Change From Baseline to End of Study in Corrected Calcium (cCa)
時間枠:Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
|
Total serum calcium was corrected if the serum albumin was < 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium. The correction formula was: Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin [g/dL]) * 0.8 |
Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
|
Participants With Low Corrected Calcium (cCA) By Category
時間枠:Timeframes: Days 8, 15, 22, 27, 29, 34, 41, 55
|
The lowest cCA value for each participant is reported. Total serum calcium was corrected if the serum albumin was < 4 g/dL or 40 g/L, otherwise cCa equals total serum calcium. The correction formula was: Corrected calcium (mg/dL) = Total calcium (mg/dL) + (4 - albumin [g/dL]) * 0.8 |
Timeframes: Days 8, 15, 22, 27, 29, 34, 41, 55
|
Baseline and Change From Baseline to End of Study in Serum Albumin
時間枠:Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
|
Serum albumin was tested at a central laboratory.
|
Baseline is the average of Day -2 and Day 1 prior to dialysis; End of Study is Day 55
|
Change From Baseline to End of Study in Serum Phosphorus
時間枠:Baseline is Day 1 prior to dialysis; End of Study is Day 55
|
Serum phosphorus was tested at a central laboratory.
|
Baseline is Day 1 prior to dialysis; End of Study is Day 55
|
Participants With Anti-etelcalcetide Antibody at Baseline and Postbaseline
時間枠:Baseline: Day 1 prior to dialysis. Postbaseline: Days 29 and 55 prior to dialysis
|
Participants with positive titers for antibodies to etelcalcetide could be asked to return to the clinical research unit to provide additional serum samples.
|
Baseline: Day 1 prior to dialysis. Postbaseline: Days 29 and 55 prior to dialysis
|
協力者と研究者
スポンサー
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 20140197
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
IPD 共有時間枠
IPD 共有アクセス基準
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
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
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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。
Placeboの臨床試験
-
Palacky University完了
-
Universidade Federal do ParaConselho Nacional de Desenvolvimento Científico e Tecnológico完了
-
Advice Pharma Group srl積極的、募集していない肥満 | 栄養障害 | 体重 | 減量 | 食生活 | 太りすぎと肥満 | 健康行動 | ダイエット、健康 | ダイエット習慣 | ライフスタイル | 栄養、健康 | 行動障害イタリア
-
University Hospital, Strasbourg, France積極的、募集していない