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

NCT03150082 | Completed Phase 1 Results

• 1 other identifier: 205730
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Infections, Bacterial

Keywords

GR37547; Cross-over; Bioequivalence; Ciprofloxacin

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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

Secondary Outcomes (23)

• Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) for Ciprofloxacin

  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

  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

  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

  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)

  Up to 4 weeks in each treatment period

Study Arms (2)

Treatment sequence: A/B

EXPERIMENTAL

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.

Drug: GR37547 tablet; Drug: Ciprofloxacin reference tablet

Treatment sequence: B/A

EXPERIMENTAL

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.

Drug: GR37547 tablet; Drug: Ciprofloxacin reference tablet

Interventions

GR37547 tablet DRUG

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.

Treatment sequence: A/B; Treatment sequence: B/A

Ciprofloxacin reference tablet DRUG

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.

Treatment sequence: A/B; Treatment sequence: B/A

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Parexel: collaborator

Study Sites (1)

GSK Investigational Site

Bloemfontein, 9301, South Africa

Location

MeSH Terms

Conditions

Bacterial Infections

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This will be an open-label study. Hence, masking will not be performed.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Crossover assignment: Subjects will receive treatment in one of the two sequences; Treatment A (GR37547 tablet) followed by Treatment B (ciprofloxacin reference tablet) or vice versa separated by a washout period of at least 7 days and not more than 14 days.

Study Record Dates

• First Submitted: May 10, 2017
• First Posted: May 11, 2017
• Study Start: August 1, 2017
• Primary Completion: August 28, 2017
• Study Completion: August 28, 2017
• Last Updated: December 19, 2018
• Results First Posted: December 19, 2018

Record last verified: 2018-06

Locations

ZA (1)