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Bioequivalence Study Between GR37547 500 Milligrams (mg) Tablet Versus Ciprofloxacin 500 mg Tablet Reference Product in Healthy Adult Subjects

2018년 6월 27일 업데이트: GlaxoSmithKline

An Open-label, Randomised, Single-dose, Two-period Cross-over Study to Evaluate Bioequivalence of GR37547 Ciprofloxacin 500 mg Tablet Versus Ciprofloxacin 500 mg Tablet Reference Product in Healthy Adult Participants Under Fasting Conditions

This two-period cross-over study will evaluate bioequivalence of GR37547 (ciprofloxacin 500 mg) tablet versus ciprofloxacin 500 mg reference tablet in healthy adult subjects under fasting conditions. Subjects will receive Treatment A (GR37547 tablet) and Treatment B (ciprofloxacin reference tablet) in crossover manner, separated by a washout period of at least 7 days and not more than 14 days. The total duration of study for each subject will be approximately 5-7 weeks. This study will enroll approximately 26 healthy adult subjects at a single center.

연구 개요

연구 유형

중재적

등록 (실제)

26

단계

  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

      • Bloemfontein,, 남아프리카, 9301
        • GSK Investigational Site

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  • Subject must be between 18 and 60 years of age inclusive, at the time of signing the informed consent.
  • Healthy, non-smoker, as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
  • A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the normal reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required,agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 19-30 kg per meter square (kg/m^2) (inclusive).
  • Healthy Male or female subjects: Male subjects: A male subject must agree to use contraception during the treatment period and for at least 5 days, after the last dose of study treatment and refrain from donating sperm during this period; Female subjects: A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment.
  • The investigator is responsible for ensuring that male and female study subjects understand how to correctly use the methods of contraception.
  • Capable of giving signed informed consent.

Exclusion Criteria:

  • History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neuromuscular, psychiatric, auto-immune or neurological disorders.
  • History of convulsions.
  • Any other condition that is capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
  • History of any malignancies or chemotherapy/radiation within the past 5 years excluding treated squamous carcinoma of the skin and adequately excised basal cell carcinoma.
  • History of kidney, heart or lung transplants.
  • History or presence of rheumatoid arthritis.
  • Presence of hypocalcaemia where the serum potassium is < lower limit of normal (LLN).
  • Presence of hypomagnesaemia where the serum magnesium is < LLN.
  • Fasting blood glucose >=7 millimoles (mmol)/liter (L).
  • Serum glucose-6-phosphate dehydrogenase < LLN.
  • Abnormal renal function, as determined by creatinine clearance and considered as clinically significant by the investigator will be excluded.
  • Alanine transaminase (ALT) >1.5x upper limit of normal (ULN).
  • Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Excessive alkalinity of the urine (potential of hydrogen [pH] >=9), as determined on Day -1.
  • Abnormal BP as determined by the investigator.
  • QT interval corrected for heart rate according to Bazett's formula (QTcB) >450 milliseconds (msec). Subjects with a known risk of QT prolongation will be excluded. For purposes of data analysis, only QTcB, will be used
  • Past or intended use of over-the-counter or prescription medication including herbal medications, within 14 days prior to dosing unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.
  • Where participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 90 days.
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Current enrolment or past participation within the last 90 days before signing of consent in this or any other clinical study involving an investigational study treatment.
  • Presence of Hepatitis B surface antigen (HBsAg) at screening or a Positive Hepatitis C antibody test result at screening.
  • Positive pre-study drug/alcohol screen.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • Regular use of known drugs of abuse.
  • Sensitivity to heparin or heparin-induced thrombocytopenia.
  • Sensitivity to any of the study treatments, or components thereof, or drug or other allergy including allergy to quinolones that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
  • Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco or nicotine-containing products within 6 months prior to screening.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 크로스오버 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Treatment sequence: A/B
Eligible subjects will be randomized to receive a single dose of Treatment A (GR37547 500 mg tablet) followed by Treatment B (ciprofloxacin 500 mg reference tablet) administered orally on Day 1 in each treatment period. The washout period will be of at least 7 days and not more than 14 days.
A single tablet of GR37547 should be taken orally with 240 mL of water. GR37547 500 mg tablet will be a white to off white capsule shape with break line on upper side and embossed "GSK500"on lower side.
A single tablet of ciprofloxacin reference should be taken orally with 240 mL of water. Ciprofloxacin 500 mg reference will be nearly white to slightly yellowish film coated oblong tablets with break line and ''CIP 500" marked on upper side and "BAYER" on lower side.
실험적: Treatment sequence: B/A
Eligible subjects will be randomized to receive a single dose of Treatment B (ciprofloxacin 500 mg reference tablet) followed by Treatment A (GR37547 500 mg tablet) administered orally. The washout period will be of at least 7 days and not more than 14 days.
A single tablet of GR37547 should be taken orally with 240 mL of water. GR37547 500 mg tablet will be a white to off white capsule shape with break line on upper side and embossed "GSK500"on lower side.
A single tablet of ciprofloxacin reference should be taken orally with 240 mL of water. Ciprofloxacin 500 mg reference will be nearly white to slightly yellowish film coated oblong tablets with break line and ''CIP 500" marked on upper side and "BAYER" on lower side.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Within a Participant Across All Treatments (AUC[0-t]) for Ciprofloxacin
기간: Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period
Blood samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of ciprofloxacin under fasted state. Pharmacokinetic analysis of ciprofloxacin was conducted using non-compartmental methods. Pharmacokinetic Population comprised of participants who completed the study and for whom primary pharmacokinetic parameters could be calculated for all treatment periods were included in the statistical pharmacokinetic analysis of the study.
Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period
Maximum Observed Plasma Concentration (Cmax) of Ciprofloxacin
기간: Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period
Blood samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of ciprofloxacin under fasted state. Pharmacokinetic analysis of ciprofloxacin was conducted using non-compartmental methods.
Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period

2차 결과 측정

결과 측정
측정값 설명
기간
Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) for Ciprofloxacin
기간: Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period
Blood samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of ciprofloxacin under fasted state. Pharmacokinetic analysis of ciprofloxacin was conducted using non-compartmental methods.
Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period
Time of Occurrence of Cmax (Tmax) for Ciprofloxacin
기간: Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period
Blood samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of ciprofloxacin under fasted state. Pharmacokinetic analysis of ciprofloxacin was conducted using non-compartmental methods. Tmax of ciprofloxacin was analyzed using a nonparametric test to compute point estimate of the median and full range.
Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period
Percentage of AUC (0-infinity) Obtained by Extrapolation (Percentage AUCex) for Ciprofloxacin
기간: Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period
Blood samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of ciprofloxacin under fasted state. Pharmacokinetic analysis of ciprofloxacin was conducted using non-compartmental methods.
Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period
Terminal Phase Half-life (t1/2) for Ciprofloxacin
기간: Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period
Blood samples were collected from participants at indicated time points in each of the treatment period 1 and 2, after administration of study treatment to investigate the pharmacokinetics of ciprofloxacin under fasted state. Pharmacokinetic analysis of ciprofloxacin was conducted using non-compartmental methods.
Pre-dose and 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 3.50, 4.50, 6.00, 8.00, 12.00, 18.00 hours post-dose on Day 1; 24.00 hours post-dose on Day 2 in each treatment period
Number of Participants With Serious Adverse Events (SAEs) and Non-serious AEs (Non-SAEs)
기간: Up to 4 weeks in each treatment period
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/ incapacity, is a congenital anomaly/ birth defect or other situations. The analysis was performed on Safety Population which comprised of all randomized participants who received at least 1 dose of study treatment. Participants were analyzed according to the treatment they actually received.
Up to 4 weeks in each treatment period
Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk Phos), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LD) at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for the analysis of clinical chemistry parameters including ALT, Alk phos, AST and LD. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Blood Urea Nitrogen (BUN) at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for the analysis of BUN. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Calcium, Chloride, Glucose, Magnesium, Potassium and Sodium at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for the analysis of clinical chemistry parameters including calcium, chloride, glucose, magnesium, potassium and sodium. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Total Bilirubin (Total Bil), Direct Bilirubin (Direct Bil) and Creatinine (Creat) at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for the analysis of clinical chemistry parameters including total bil, direct bil and creat. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Total Protein at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for the analysis of total Protein. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Platelets, Neutrophils, Monocytes, Lymphocytes, Leucocyte, Eosinophils and Basophils at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for evaluation of hematology parameters including platelets, neutrophils, monocytes, lymphocytes, leucocyte, eosinophils and basophils. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Mean Corpuscular Volume (MCV) at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for evaluation of MCV. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Mean Corpuscular Hemoglobin (MCH) at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for evaluation of MCH. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb) at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for evaluation of hematology parameters including MCHC and Hb. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Percent Reticulocytes at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for evaluation of percent reticulocytes. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Hematocrit at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for evaluation of hematocrit. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Erythrocyte Count at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2 for evaluation of erythrocyte count. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Number of Participants With Clinically Significant Abnormal Findings for Urinalysis
기간: Up to Day 2 of each treatment period
Urine samples were collected from participants on Day -1 and Day 2 of each treatment period 1 and 2. The number of participants with abnormal (clinically significant) findings for urinalysis have been presented.
Up to Day 2 of each treatment period
Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters
기간: Up to Day 2 of each treatment period
A single 12-lead ECGs was obtained on Day 1 and Day 2 of each treatment period 1 and 2 using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT corrected (QTc) intervals. The number of participants with abnormal (clinically significant) findings for ECG parameters have been presented.
Up to Day 2 of each treatment period
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time-points
기간: Up to Day 2 of each treatment period
Blood pressure of participants was measured on Day 1 and Day 2 of each treatment period 1 and 2 in a supine position after 5 minutes rest. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Respiratory Rate at Indicated Time-points
기간: Up to Day 2 of each treatment period
Respiratory rate of participants was measured on Day 1 and Day 2 of each treatment period 1 and 2 in a supine position after 5 minutes rest. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Pulse Rate at Indicated Time-points
기간: Up to Day 2 of each treatment period
Pulse rate of participants was measured on Day 1 and Day 2 of each treatment period 1 and 2 in a supine position after 5 minutes rest. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period
Body Temperature at Indicated Time-points
기간: Up to Day 2 of each treatment period
Body temperature of participants was measured on Day 1 and Day 2 of each treatment period 1 and 2 in a supine position after 5 minutes rest. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Up to Day 2 of each treatment period

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여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

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연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2017년 8월 1일

기본 완료 (실제)

2017년 8월 28일

연구 완료 (실제)

2017년 8월 28일

연구 등록 날짜

최초 제출

2017년 5월 10일

QC 기준을 충족하는 최초 제출

2017년 5월 10일

처음 게시됨 (실제)

2017년 5월 11일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2018년 12월 19일

QC 기준을 충족하는 마지막 업데이트 제출

2018년 6월 27일

마지막으로 확인됨

2018년 6월 1일

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미국 FDA 규제 의약품 연구

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미국 FDA 규제 기기 제품 연구

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이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

GR37547 tablet에 대한 임상 시험

구독하다