Last updated: 11/03/2018 19:16:45
Bioequivalence of two levothyroxine tablet formulations in healthy Indian volunteers
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: Bioequivalence of two levothyroxine tablet formulations in healthy Indian volunteers: A single-dose, randomized, open-label, crossover study
Trial description: 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.
Primary purpose:
Other
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Maximum observed concentration (Cmax) of levothyroxine (T4) and tri-iodothyronine (T3), after adjustment by Baseline levels of endogenous T4 from test and reference formulations of thyroxine sodium
Timeframe: Pre-dose (-0.5, -0.25 and 0 hours) and post dose (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) of each treatment period (up to 76 days)
Area under concentration-time curve at 0-48 hours (AUC0-48) of T4 and T3, after adjustment by Baseline levels of endogenous T4 from test and reference formulations of thyroxine sodium
Timeframe: Pre-dose (-0.5, -0.25 and 0 hours) and post dose (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) of each treatment period (up tp 76 days)
Secondary outcomes:
Cmax of T4 without adjustment by Baseline levels of endogenous T4 and T3 from test and reference formulations of thyroxine sodium
Timeframe: Pre-dose (-0.5, -0.25 and 0 hours) and post dose (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) of each treatment period (up tp 76 days)
AUC0-48 of T4 without adjustment by baseline levels of endogenous T4 and T3 from test and reference formulations of thyroxine sodium
Timeframe: Pre-dose (-0.5, -0.25 and 0 hour) and post dose (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) of each treatment period (up tp 76 days)
Time of occurrence of Cmax (Tmax) and terminal phase half life (T-half) of T4 and T3 with and without adjustment from test and reference formulations of thyroxine sodium
Timeframe: Pre-dose (-0.5, -0.25 and 0 hour) and post dose (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) of each treatment period (up tp 76 days)
Elimination constant (Kel) of T4 and T3, with and without adjustment by baseline levels of endogenous T4 from test and reference formulations of Thyroxine sodium
Timeframe: Pre-dose (-0.5, -0.25 and 0 hour) and post dose (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) of each treatment period (up tp 76 days)
Serum TSH levels before and after treatment with test and reference formulations of thyroxine sodium
Timeframe: Pre-dose (-0.5, -0.25 and 0 hours) and post dose (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) of each treatment period (up tp 76 days)
Number of participants with adverse events (AEs) and serious adverse events (SAE)
Timeframe: AEs was collected from the start of study treatment and until the follow-up contact (approximately 76 days)
Interventions:
Enrollment:
26
Primary completion date:
2012-16-04
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Hypothyroidism
Product
levothyroxine sodium
Collaborators
Not applicable
Study date(s)
January 2012 to April 2012
Type
Interventional
Phase
Not applicable
Participation criteria
Sex
Male
Age
18 - 50 years
Accepts healthy volunteers
Yes
- 1.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).
- 2.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.
- 1.A positive pre-study urine drug screen.
- 2.A positive test for HIV antibody.
Inclusion and exclusion criteria
Inclusion criteria:
- 1.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). 2.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. 3.Body weight more than or equal to 60 kg and BMI within the range 18.5-24.9 kg/m2 (inclusive). 4.Availability of a study volunteer for the entire study period and willingness to adhere to protocol requirements as evidenced by written informed consent.
Exclusion criteria:
- 1.A positive pre-study urine drug screen. 2.A positive test for HIV antibody. 3.Subject has clinically significant abnormal values of laboratory parameters. 4.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. 5.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). 6.Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 7.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. 8.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. 9.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. 10.Unwillingness or inability to follow the procedures outlined in the protocol. 11.Subject is mentally or legally incapacitated or the subject is incapable of understanding the informed consent. 12.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. 13.History of sensitivity to heparin or heparin-induced thrombocytopenia. 14.Regular use of tobacco- or nicotine-containing products within 6 months prior to screening. 15.Subject is intolerant to venipuncture. 16.Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice [and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices] from 7 days prior to the first dose of study medication.
Trial location(s)
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2012-16-04
Actual study completion date
2012-16-04
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
Participate in clinical trial
Access to clinical trial data by researchers
Visit website