Study to Determine the Relative Bioavailability, Single and Repeat Dose Pharmacokinetics, Safety and Tolerability of BOS172767 Enantiomers in Healthy Subjects
2020年11月17日 更新者:Boston Pharmaceuticals
A Phase 1 Study to Determine the Relative Bioavailability of BOS172767 Enantiomer E1 and E2 and the Single and Repeat Dose Pharmacokinetics, Safety and Tolerability of BOS172767 Selected Enantiomer in Healthy Subjects
Part 1 of the study evaluates the safety and tolerability as well as pharmacokinetic properties of a single oral dose of BOS172767 enantiomer E1 and BOS172767 enantiomer E2 following administration to healthy participants.
Part 2 of the study was to be conducted to assess the safety and tolerability as well as pharmacokinetic properties of one selected enantiomer (BOS172767-Ex) following multiple ascending doses over 14 days of dosing in healthy participants.
調査の概要
詳細な説明
The study design of Part 1 was a double-blind, placebo-controlled, randomized, single-dose, two-way crossover, followed by two sequential ascending dose periods in 12 healthy participants.
Part 2 was designed to be a double-blind, placebo-controlled, randomized multiple ascending dose (MAD) study in 36 healthy participants (12 per study cohort).
Part 2 was to progress following completion of Part 1, but was not conducted.
研究の種類
介入
入学 (実際)
12
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Nottingham、イギリス
- Quotient Sciences
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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~50年 (大人)
健康ボランティアの受け入れ
はい
受講資格のある性別
全て
説明
Inclusion Criteria:
- Healthy males or healthy females of non-childbearing potential
- Age 18 to 50 years at the time of signing informed consent
- Body mass index (BMI) of 18.0 to 32.0 kilograms per meters squared (kg/m^2) as measured at screening
- Must have been willing and able to communicate and participate in the whole study
- Must have provided written informed consent
- Must have agreed to adhere to the contraception requirements for this study
Exclusion Criteria:
- Participants who received any investigational medicinal product (IMP) in a clinical research study within the 90 days prior to Day 1
- Participants who were study site employees, or immediate family members of a study site or sponsor employee
- Participants who had previously been enrolled and dosed in this study. Participants who had taken part in Part 1 were not permitted to take part in Part 2. Participants who had taken part in study QCL118174/BOS172767-01 (NCT03464058) were allowed to participate in this study.
- History of any drug or alcohol abuse in the past 2 years
- Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = 1/2 pint beer, or a 25 milliliter [mL] shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type)
- A confirmed positive alcohol breath test at screening or admission
- Current smokers and those who had smoked within the last 6 months. A confirmed breath carbon monoxide reading of greater than 20 parts per million (ppm) at screening or admission.
- Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 6 months
- Females of childbearing potential including those who were pregnant or lactating (all female participants must have had a negative serum pregnancy test at screening and had a negative urine pregnancy test at all other time points). A woman was considered of childbearing potential unless she was permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or was postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration ≥40 International Units per Liter [IU/L])
- Participants who did not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
- Clinically significant abnormal clinical chemistry, haematology, or urinalysis as judged by the investigator. Participants with Gilbert's Syndrome were not allowed.
- Participants with alanine aminotransferase (ALT) > 1.5 x upper limit of normal (ULN) at screening (Part 1 and Part 2) or Day -1 (Part 2 only)
- Confirmed positive drugs of abuse test result
- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus (HIV) results
- Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <70 milliliters per minute (mL/min) using the Cockcroft-Gault equation
- History of clinically significant cardiovascular, renal, hepatic, chronic respiratory, or gastrointestinal disease (including gall stones and/or cholecystectomy), or neurological or psychiatric disorder, as judged by the investigator
- Serious adverse reaction or serious hypersensitivity to any drug or the IMP excipients
- Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever was allowed unless it was active.
- Donation or loss of greater than 400 mL of blood within the previous 3 months
- Participants who were taking, or had taken, any prescribed or over-the-counter drug (other than 4 grams of paracetamol per day and/or hormone replacement therapy [HRT]) or herbal remedies in the 14 days before IMP administration. Exceptions may have applied on a case by case basis, if considered not to have interfered with the objectives of the study, as determined by the principal investigator.
- Participants who had any ongoing fungal infections (stable toe nail onchomycosis was allowed)
- Failure to satisfy the investigator of fitness to participate for any other reason
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:基礎科学
- 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:トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的:Part 1: Regimens AB(CD)
Participants received 50 milligrams (mg) BOS172767 E1 tablets or matching placebo (Regimen A) in the fasted state in Period 1, followed by 50 mg BOS172767 E2 tablets or matching placebo (Regimen B) in the fasted state in Period 2. In Period 3 and 4, participants received BOS172767-Ex (selected enantiomer from Part 1 [E1 or E2]) tablets or matching placebo (Regimens C and D, respectively) from Regimen A or B in the fasted state.
The Period 3 and 4 dose was selected after review of data from Periods 1 and 2. In each Period, dosing occurred on Day 1, and there was a washout period of at least 10 days or 5 half-lives of the parent (whichever is greater) between each dose of investigational medicinal product.
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経口錠剤
Oral tablets
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実験的:Part 1: Regimens BA(CD)
Participants received 50 milligrams (mg) BOS172767 E2 tablets or matching placebo (Regimen B) in the fasted state in Period 1, followed by 50 mg BOS172767 E1 tablets or matching placebo (Regimen A) in the fasted state in Period 2. In Period 3 and 4, participants received BOS172767-Ex (selected enantiomer from Part 1 [E1 or E2]) tablets or matching placebo (Regimens C and D, respectively) from Regimen A or B in the fasted state.
The Period 3 and 4 dose was selected after review of data from Periods 1 and 2. In each Period, dosing occurred on Day 1, and there was a washout period of at least 10 days or 5 half-lives of the parent (whichever is greater) between each dose of investigational medicinal product.
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経口錠剤
Oral tablets
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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 |
|---|---|---|
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Part 1: Relative bioavailability of E1 versus E2 (Frel; exposure) of a single oral dose of BOS172767 enantiomer 1 (E1) and enantiomer 2 (E2) following administration to healthy participants based on Cmax, AUC(0-last), and AUC (0-inf)
時間枠:24 hours post-dose for each of the four 6-day Periods
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Cmax is defined as the maximum observed concentration.
AUC(0-last) is defined as the area under the curve from 0 time to the last measurable concentration.
AUC (0-inf) is defined as the area under the curve from 0 time extrapolated to infinity.
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24 hours post-dose for each of the four 6-day Periods
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Part 1: Number of participants with any treatment-emergent adverse event
時間枠:up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
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up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
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Part 1: Number of participants with abnormal, clinically significant physical examination findings
時間枠:up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
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up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
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Part 1: Number of participants with abnormal, clinically significant safety laboratory test findings
時間枠:up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
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up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
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Part 1: Number of participants with abnormal, clinically significant vital sign values
時間枠:up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
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up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
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Part 1: Number of participants with abnormal, clinically significant electrocardiogram findings
時間枠:up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
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up to Day 6 of each Period; up to a 10-day Follow-up Period after last dose (up to Study Day 59)
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Part 1: Plasma concentration of BOS172767 enantiomers 1 and 2
時間枠:24 hours post-dose for each of the four 6-day Periods
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24 hours post-dose for each of the four 6-day Periods
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Part 1: Slope estimates (β) from the power model analysis on Cmax, AUC(0-last), and AUC(0-inf), as a measure of dose proportionality
時間枠:24 hours post-dose for each of the four 6-day Periods
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24 hours post-dose for each of the four 6-day Periods
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Part 2: Plasma concentration of BOS172767-Ex (enantiomer E1 or E2)
時間枠:24 hours post-dose
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24 hours post-dose
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Part 2: Number of participants with any treatment-emergent adverse event
時間枠:up to Day 24 of Part 2 (up to approximately 18 study weeks)
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up to Day 24 of Part 2 (up to approximately 18 study weeks)
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Part 2: Number of participants with abnormal, clinically significant physical examination findings
時間枠:up to Day 24 of Part 2 (up to approximately 18 study weeks)
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up to Day 24 of Part 2 (up to approximately 18 study weeks)
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Part 2: Number of participants with abnormal, clinically significant safety laboratory test findings
時間枠:up to Day 24 of Part 2 (up to approximately 18 study weeks)
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up to Day 24 of Part 2 (up to approximately 18 study weeks)
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Part 2: Number of participants with abnormal, clinically significant vital sign values
時間枠:up to Day 24 of Part 2 (up to approximately 18 study weeks)
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up to Day 24 of Part 2 (up to approximately 18 study weeks)
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Part 2: Number of participants with abnormal, clinically significant electrocardiogram findings
時間枠:up to Day 24 of Part 2 (up to approximately 18 study weeks)
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up to Day 24 of Part 2 (up to approximately 18 study weeks)
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Part 2: Slope estimates (β) from the power model analysis on Cmax, AUC(0-last), and AUC(0-inf), as a measure of dose proportionality
時間枠:24 hours post-dose
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24 hours post-dose
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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)
2019年9月12日
一次修了 (実際)
2020年1月22日
研究の完了 (実際)
2020年1月22日
試験登録日
最初に提出
2020年8月12日
QC基準を満たした最初の提出物
2020年8月12日
最初の投稿 (実際)
2020年8月14日
学習記録の更新
投稿された最後の更新 (実際)
2020年11月18日
QC基準を満たした最後の更新が送信されました
2020年11月17日
最終確認日
2020年11月1日
詳しくは
本研究に関する用語
その他の研究ID番号
- BOS172767-02
- 2019-002289-11 (EudraCT番号)
- QSC201870 (その他の識別子:Quotient Sciences)
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?
いいえ
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。
はい
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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