Bioequivalence of Two Levothyroxine Tablet Formulations in Healthy Indian Volunteers

NCT01536678 | Completed Phase 4

• 1 other identifier: 116526
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

GSK markets a drug called levothyroxine or T4 that is used to treat patients with hypothyroidism. Till date, the active drug substance or active pharmaceutical ingredient (API) for levothyroxine tablets marketed in India has been obtained from a particular source. GSK India proposes to change the source of the API from the existing source to a new source. Some patients may experience a change in clinical effect when switched from one formulation to another. Therefore this study is being done to understand whether a change in API in levothyroxine tablet has any impact on the clinical effect of the drug. The purpose of this study is to: See how quickly the levothyroxine tablet from the new source (single dose of 600mcg) enters the bloodstream, is distributed in the body, broken down and removed compared to the levothyroxine tablet from the existing source (single dose of 600mcg). Study the effect of single 600mcg doses of levothyroxine tablet from new source and levothyroxine tablet from existing source on TSH level in the blood. Study the safety and side effects of single 600mcg doses of levothyroxine tablet from new source and levothyroxine tablet from existing source.

Conditions

Hypothyroidism

Outcome Measures

Primary Outcomes (1)

• Maximum observed concentration (Cmax) and Area under concentration-time curve [AUC (0-48)]

  Cmax and AUC (0-48) will be determined from the individual and mean serum concentration-time profiles of total T4 and T3, after adjustment by baseline levels of endogenous T4.

  -0.5, -0.25, 0, 0.5, 1.00, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 18.00, 24.00 and 48.00 hours.

Secondary Outcomes (7)

• Cmax

  -0.5, -0.25, 0, 0.5, 1.00, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 18.00, 24.00 and 48.00 hours.

• AUC (0-48)

  -0.5, -0.25, 0, 0.5, 1.00, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 18.00, 24.00 and 48.00 hours.

• Tmax

  -0.5, -0.25, 0, 0.5, 1.00, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 18.00, 24.00 and 48.00 hours.

• Kel

  -0.5, -0.25, 0, 0.5, 1.00, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 18.00, 24.00 and 48.00 hours.

• t1/2

  -0.5, -0.25, 0, 0.5, 1.00, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00, 18.00, 24.00 and 48.00 hours.

Study Arms (2)

Test formulation of levothyroxine

ACTIVE COMPARATOR

Single dose of 600 mcg of levothyroxine administered in dosing period 1 or 2..

Drug: Levothyroxine

Reference formulation of levothyroxine

ACTIVE COMPARATOR

Single dose of 600 mcg of levothyroxine administered in dosing period 1 or 2.

Drug: Levothyroxine

Interventions

Levothyroxine DRUG

Single dose of 600mcg of test formulation of levothyroxine administered in dosing period 1 or 2.

Test formulation of levothyroxine

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, 12 lead ECG and chest-x-ray. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Medical Investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with total T4 (4.5 -12.0 µg/dL), T3 (0.79 - 1.49 ng/mL) and TSH (21 weeks - 20 years: 0.7 - 6.4 µIU/mL, 21 - 54 years: 0.4 - 4.2 µIU/mL) values outside the normal range should always be excluded from enrollment (Interpath Lab Instructions, 2010).
• Males between 18 and 50 years of age (both inclusive), who are willing to participate in the study and provide a written signed and dated informed consent.
• Body weight more than or equal to 60 kg and BMI within the range 18.5-24.9 kg/m2 (inclusive).
• Availability of a study volunteer for the entire study period and willingness to adhere to protocol requirements as evidenced by written informed consent.

You may not qualify if:

• A positive pre-study urine drug screen.
• A positive test for HIV antibody.
• Subject has clinically significant abnormal values of laboratory parameters.
• Regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>21 units. One unit is equivalent to 8 g of alcohol: a half-pint (\~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject safety.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator contraindicates their participation.
• Where participation in another study would result in donation of blood or blood products in excess of 350 ml within a 90 day period prior to this study.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated or the subject is incapable of understanding the informed consent.
• Subject has any evidence of impaired renal, hepatic, cardiac, lung or gastrointestinal function. Study volunteers with a history of tuberculosis, epilepsy, asthma (during past 5 years), diabetes, psychosis or glaucoma will not be eligible for the study.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Subject is intolerant to venipuncture.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Hyderabad, 500051, India

Location

MeSH Terms

Conditions

Hypothyroidism

Interventions

Thyroxine

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2012
• First Posted: February 22, 2012
• Study Start: January 1, 2012
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: February 11, 2013

Record last verified: 2012-10

Locations

IN (1)