Pharmacokinetics Of Orally Administered Fx-1006A In Subjects With Hepatic Dysfunction
This is a Phase I, open-label, single-dose study designed to assess the effects of hepatic dysfunction on the PK of orally administered Fx-1006A 20 mg soft gelatin capsules.
An adaptive 2-stage study design will be implemented. Initially (Stage 1), a group of 9 subjects with moderate hepatic dysfunction (Child-Pugh score of 7-9, inclusive) followed by a group of 9 healthy volunteer subjects with normal hepatic function who are comparable in age, gender, and weight to the hepatically impaired subjects will be enrolled to receive a single oral 20 mg dose of Fx-1006A each.
Data obtained from the first 2 groups will be analyzed and reviewed by the Sponsor to determine whether Fx-1006A PK is altered by hepatic dysfunction. If it is determined that hepatic dysfunction affects Fx-1006A PK, then Stage 2 will be commenced. During Stage 2, a group of 9 subjects with mild impairment (Child-Pugh score of 5-6, inclusive) will be enrolled to receive a single oral 20 mg dose of Fx-1006A each. Additional subjects with normal hepatic function may be enrolled to ensure appropriate demographic matching to the mild hepatically impaired subjects, with respect to age, gender, and weight.
During Screening, subjects will provide written informed consent to participate in the study and be reviewed against the study entrance criteria (including assessment of hepatic function) to determine eligibility. All subjects will provide blood and urine samples for clinical laboratory testing, drug testing, and pregnancy testing to determine eligibility.
Subjects who meet the entrance criteria during Screening will check in to the clinical site 1 day prior to dosing (Day 0) in the evening, and will be reviewed against the entrance criteria to confirm eligibility. Subjects will remain inpatient overnight for pre-dose assessments. Subjects will be fasted for a minimum of 8 hours prior to dosing the following day (water is allowed).
The single Fx-1006A dose will be administered on Day 1 under supervision of the Investigator or appropriate clinical site staff. Subjects will remain fasted for 4 hours after dosing (water is allowed) and will remain inpatient overnight for safety monitoring and PK sample collection.
Subjects will be discharged on Day 2, after they have completed the study procedures and the Investigator has determined that the subject is clinically stable. Subjects will return to the clinical site for out-patient visits on Days 3, 4, 6, 9, 12, and 16 for safety evaluations and PK sample collection. Day 16 will be the end of study visit.
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
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Port Elizabeth
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Newton Park、Port Elizabeth、南アフリカ、6045
- Pfizer Investigational Site
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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:
All Subjects
- Subject is male or female (female subjects must be of non-child-bearing potential or willing to use a medically acceptable form of birth control during the study).
- Subject is between 18 to 70 years of age, inclusive.
- Subject is a cigarette smoker, consuming less than 15 cigarettes per day.
- Subject has given written informed consent.
Hepatic Dysfunction Subjects:
Subject has hepatic dysfunction:
- Study Stage 1: Subject has moderate hepatic dysfunction (Child-Pugh score of 7-9, inclusive)
- Study Stage 2 (if commenced): Subject has mild hepatic dysfunction (Child-Pugh score of 5-6, inclusive)
- Subject's hepatic disease is deemed stable by the Investigator.
- Subject's pre-study clinical laboratory findings are within normal range or if outside of the normal range, deemed associated with underlying hepatic dysfunction or not clinically significant in the opinion of the Investigator and the sponsor.
Normal Hepatic Function Subjects:
Subject is considered to be in good health in the opinion of the Investigator, as determined by:
- A pre-study physical examination with no clinically significant abnormalities
- Vital signs within normal ranges
- An ECG with no clinically significant abnormalities
- Subject's pre-study clinical laboratory findings are within normal range or if outside of the normal range not deemed clinically significant in the opinion of the Investigator and the Sponsor.
Exclusion Criteria:
- Subject has had a clinically significant illness in the four (4) weeks before screening.
- Subject shows evidence of a clinically significant underlying medical condition, including renal, cardiovascular, or metabolic dysfunction that, in the opinion of the Investigator, would represent a risk of study participation.
- Subject has any other clinically significant laboratory abnormality, as determined by the Investigator, within 21 days before dosing on Day 1.
- Subject has a history of clinically important disease that, in the opinion of the investigator, may put the subject at risk because of participation in this study.
- Subject is enrolled or plans to enroll in another clinical trial during this study or has received an investigational drug/device within 60 days before Day 1.
- Subject is known to be hepatitis B surface antigen (HbsAg) positive, anti-hepatitis C antibody (anti-HCV) positive, or human immunodeficiency virus (HIV) positive, or has any positive result during Screening.
- Subject has a history of alcohol abuse, or illicit drug use, physical dependence to any opioid, or drug abuse or addiction.
- Subject has a history of significant mental illness.
- Subject has positive urine drug screen test results within 21 days before Day 1, excluding alcohol. Alcohol consumption is not permitted within 72 hours before Day 1.
- Subject has a history of complications associated with providing blood samples.
- Subject reports donating greater than 150 mL of blood or donating plasma via plasmapheresis within 28 days prior to enrollment. All subjects will be advised not to donate blood for four weeks after completing the study.
Hepatic Dysfunction Subjects:
- Subject has an encephalopathy grade > 1.
- Subject has any clinically significant laboratory abnormality not associated with underlying hepatic impairment, as determined by the Investigator, within 21 days before dosing on Day 1.
- Unless being used to treat the subject's underlying hepatic disease, the subject has taken an over the counter (OTC) medication (including non-steroidal anti-inflammatory drugs (NSAIDs) or herbal preparations) within 48 hours before Day 1.
Normal Hepatic Function Subjects:
- Use of prescription medications in the 14 days prior to Day 1.
- Subject has taken an OTC medication (including NSAIDs or herbal preparations) within 48 hours before Day 1.
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:基礎科学
- 割り当て:非ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ:Mild and Moderate Hepatic Dysfunction
Patients with mild and moderate hepatic dysfunction
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A single oral 20 mg dose of Fx-1006A will be administered on Day 1 followed by 16 days of follow-up.
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アクティブコンパレータ:Healthy Volunteers
Healthy volunteers
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A single oral 20 mg dose of Fx-1006A will be administered on Day 1 followed by 16 days of follow-up.
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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 |
時間枠 |
|---|---|
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Pharmacokinetic parameters are AUC0-last and Cmax
時間枠:Daily
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Daily
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Parameters are AUC0-inf, Cl, Tmax, t1/2; AUC, Cmax, and Cl will also be expressed in terms of unbound concentrations using the free fraction determined from protein binding assessments
時間枠:Daily
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Daily
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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
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 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
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
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