A Study of Cephalexin Suspension in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02123459
• Collaborator: Investigacion Farmacologica y Biofarmaceutica, S.A. de C.V. (Other)
• Enrollment: 28
• Location: 1
• Arms: 2

Study Details

Study Description

Brief Summary

The purpose of this study is to compare two different preparations of an antibiotic called cephalexin to determine if they are essentially the same. The study has two periods. Participants will receive one preparation of cephalexin in each period. At least 7 hours will pass between the study periods. The study is expected to last about 2 days for each participant, not including screening or follow-up.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Cephalexin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Randomized, Open-label, Two-period, Two-treatment, Two-sequence, Crossover Study to Evaluate the Bioequivalence of Single Doses of Two Oral Preparations in Suspension With 250 mg/5 ml of Cephalexin (Keflex® Liquido Made in Mexico by Eli Lilly y Compañía de México, S.A. de C.V. vs. Keflex® Liquido Made by Antibioticos do Brasil Ltda for Eli Lilly y Compañía de México, S.A. de C.V.) in Fasting Healthy Volunteers
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cephalexin (Reference) Cephalexin manufactured in Mexico by Eli Lilly administered once orally in one of two study periods	Drug: Cephalexin; Administered orally; Other Names: Keflex®
Active Comparator: Cephalexin (Test) Cephalexin manufactured in Brasil by Antibioticos do Brasil Ltda administered once orally in one of two study periods	Drug: Cephalexin; Administered orally; Other Names: Keflex®

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of Cephalexin Following a Single Dose [Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, and 7.0 hours in each period]

Secondary Outcome Measures

1. Pharmacokinetics: Maximum Concentration (Cmax) of Cephalexin [Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, and 7.0 hours in each period]

2. Pharmacokinetics: Time to Reach Maximum Observed Concentration (Tmax) of Cephalexin Following a Single Dose Maximum [Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, and 7.0 hours in each period]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Participation will be voluntary.

• The body mass index of participants should be between 18-27.

• Participants should have a good health status.

• Limits of variation allowed within normal values at screening will be: blood pressure (seated) up to 139 millimeters of mercury (mm Hg), for systolic, and up to 89 mm Hg for diastolic; heart rate between 60 and 100 beats per minute, and respiratory rate between 14 and 20 breaths per minute.

• Hepatitis B and C and human immunodeficiency virus (HIV) negative.

• Drug abuse or alcohol detection test approximately 12 hours before administering the study medication.

• Serum pregnancy test (beta human chorionic gonadotropin) at screening and urine pregnancy test approximately 12 hours before administering the study medication.

Exclusion Criteria:

• Participants with any clinically significant abnormality in their vital sign constants recorded at screening.

• Sponsor´s and/or site employees.

• Abnormal 12 lead electrocardiogram (ECG) that in the opinion of the investigator places the participant at an unacceptable risk for study participation, Bazett corrected QR interval (QTcB) > 470 millisecond (msec) for women and > 450 msec for men.

• Participants with history of cardiovascular, renal, hepatic, muscular, metabolic, gastrointestinal diseases, including constipation, neurological, endocrine, hematopoietic diseases, or any type of anemia, asthma, mental disease, or other organic abnormalities.

• Participants with a creatinine clearance < 80 mL/min based on the Cockcroft-Gault equation.

• Participants requiring any medication during the study, apart from the medication which is being studied.

• Participants with history of dyspepsia, gastritis, esophagitis, duodenal or gastric ulcer.

• Participants who have been exposed to medications known as hepatic enzyme inducers or inhibitors or who have been taking potentially toxic medications within the 30 days prior.

• Participants who have received any medication, including vitamins (with or without medical prescription) or herbal-based remedies 30 days (or 7 half-lives) prior to the beginning of the study.

• Participants who have been hospitalized for any condition within six months to the beginning of the study.

• Participants who have received investigational drugs within the 60 days prior to the study.

• Participants allergic to any medication, food, or substance.

• Participants who require therapy with nephrotoxic drugs.

• Participants who have donated 450 mL of blood or more within the 60 days prior to the beginning of the study.

• Participants with history of drug and alcohol abuse.

• Participants with special diet requirement for any cause.

• Participants with positive to pregnancy test or are breastfeeding.

• Participants on hormonal treatment by any route.

• Participants who have not been recorded in the page of the Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mexico City		Mexico	14610

Sponsors and Collaborators

• Eli Lilly and Company
• Investigacion Farmacologica y Biofarmaceutica, S.A. de C.V.

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02123459
• Other Study ID Numbers: 15314; A3Q-ME-AFBQ
• First Posted: Apr 25, 2014
• Last Update Posted: May 27, 2015
• Last Verified: May 1, 2015

• Additional relevant MeSH terms: Cephalexin

Study Results

Participant Flow

Arm/Group Title	Cephalexin Dosing Sequence AB	Cephalexin Dosing Sequence BA
Arm/Group Description	Each participant was administered Cephalexin A formulation (Treatment A, Reference - 1 occasion) and Cephalexin B formulation (Treatment B, Test - 1 occasion).There was an interval of 1 day between doses.	Each participant was administered Cephalexin B formulation (Treatment B, Test - 1 occasion) and Cephalexin A formulation (Treatment A, Reference - 1 occasion).There was an interval of 1 day between doses.
Period Title: Period 1 (7 Days)
STARTED	14	14
COMPLETED	14	14
NOT COMPLETED	0	0
Period Title: Period 1 (7 Days)
STARTED	14	14
COMPLETED	13	14
NOT COMPLETED	1	0
Period Title: Period 1 (7 Days)
STARTED	13	14
COMPLETED	13	14
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	Each participant was administered Cephalexin A formulation (Treatment A, Reference - 1 occasion) and Cephalexin B formulation (Treatment B, Test - 1 occasion).
Overall Participants	28
Age (Years) [Median (Standard Deviation) ]
Median (Standard Deviation) [Years]	30.9 (9.57)
Sex: Female, Male (Count of Participants)
Female	24 85.7%
Male	4 14.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	28 100%
Not Hispanic or Latino	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Mexico	28 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of Cephalexin Following a Single Dose
Time Frame	Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, and 7.0 hours in each period

Outcome Measure Data

Analysis Population Description

All participants who had at least one study treatment and had evaluable pharmacokinetic (PK) data.

Arm/Group Title	Cephalexin (Reference)	Cephalexin (Test)
Arm/Group Description	Cephalexin (Treatment A) manufactured in Mexico by Eli Lilly administered once orally in one of two study periods	Cephalexin (Treatment B) manufactured in Brasil by Antibioticos do Brasil Ltda administered once orally in one of two study periods
Measure Participants	27	27
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per milliliter(h*μg/mL)]	29.539 (22.919)	35.857 (14.452)

2. Secondary Outcome

Title	Pharmacokinetics: Maximum Concentration (Cmax) of Cephalexin
Time Frame	Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, and 7.0 hours in each period

Outcome Measure Data

Analysis Population Description

All participants who had at least one study treatment and had evaluable pharmacokinetic (PK) data.

Arm/Group Title	Cephalexin (Reference)	Cephalexin (Test)
Arm/Group Description	Cephalexin (Treatment A) manufactured in Mexico by Eli Lilly administered once orally in one of two study periods	Cephalexin (Treatment B) manufactured in Brasil by Antibioticos do Brasil Ltda administered once orally in one of two study periods
Measure Participants	27	27
Geometric Mean (Geometric Coefficient of Variation) [μg/mL]	10.378 (25.616)	12.610 (23.867)

3. Secondary Outcome

Title	Pharmacokinetics: Time to Reach Maximum Observed Concentration (Tmax) of Cephalexin Following a Single Dose Maximum
Time Frame	Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, and 7.0 hours in each period

Outcome Measure Data

Analysis Population Description

All participants who had at least one study treatment and had evaluable pharmacokinetic (PK) data.

Arm/Group Title	Cephalexin (Reference)	Cephalexin (Test)
Arm/Group Description	Cephalexin (Treatment A) manufactured in Mexico by Eli Lilly administered once orally in one of two study periods	Cephalexin (Treatment B) manufactured in Brasil by Antibioticos do Brasil Ltda administered once orally in one of two study periods
Measure Participants	27	27
Median (Standard Deviation) [Hours]	1.500 (0.881)	1.500 (0.758)

Adverse Events

Arm/Group Title	Cephalexin (Reference)		Cephalexin (Test)
Arm/Group Description	Cephalexin (Treatment A) manufactured in Mexico by Eli Lilly administered once orally in one of two study periods Cephalexin: Administered orally		Cephalexin (Treatment B) manufactured in Brasil by Antibioticos do Brasil Ltda administered once orally in one of two study periods Cephalexin: Administered orally
All Cause Mortality
	Cephalexin (Reference)		Cephalexin (Test)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cephalexin (Reference)		Cephalexin (Test)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Cephalexin (Reference)		Cephalexin (Test)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		2/28 (7.1%)
Gastrointestinal disorders
Nausea	0/28 (0%)	0	2/28 (7.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.