HypothyroidismPhase 4NCT01536678
Bioequivalence of Two Levothyroxine Tablet Formulations in Healthy Indian Volunteers
A Phase 4 study testing Levothyroxine in people with Hypothyroidism, run by GlaxoSmithKline at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hypothyroidism
- What is being tested?
- Levothyroxine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteIndia
- Study dates
- Jan 2012to Apr 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Bioequivalence of Two Levothyroxine Tablet Formulations in Healthy Indian Volunteers: A Single-dose, Randomized, Open-label, Crossover Study
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:
Read more
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.
Read the detailed description
Levothyroxine (T4) is used to treat patients with hypothyroidism and may often result in lifelong therapy. Its physiologically active metabolite is tri-iodothyronine (T3). Levothyroxine is also endogenously produced in the body. Since small changes in levothyroxine administration (e.g. change in brand or formulation) can cause significant changes in serum thyroid stimulating hormone (TSH) concentrations, precise and accurate TSH control is critical to avoid potential adverse iatrogenic effects. Till date, the active pharmaceutical ingredient (API) for levothyroxine tablets marketed in India has been sourced from company 1. GSK India proposes to change the source of the API from the existing source (company 1) to to new source (company 2). In view of this change in the source of API, it is essential to determine whether it has any impact on drug product performance based on pharmacokinetic (PK) measures of total serum T4 and total serum T3 of the to-be-marketed formulation of levothyroxine (test formulation from company 2, Treatment A) relative to the formulation currently in the market (reference formulation from company 1, Treatment B).
This will be a single-center, open-label, two-period, two-treatment, two-sequence, randomized, single-dose, crossover study. 26 healthy adult males will be randomized to receive a single dose (6 x 100mcg tablets = 600mcg) of the test formulation of levothyroxine and reference formulation of levothyroxine separately in each treatment period. There will be two treatment sequences (AB, BA) and a 35 day washout between the two treatment periods.
The study will be conducted at BA/BE facility after approval from an independent ethics committee. Subjects will have a screening visit within 21 days prior to the first dose of study drug, two treatment periods with each containing a single dose of study drug, followed by 48 hours of serial PK sample collection. Subjects will check out of the unit on Day 3 (at 7am) after collection of the 48 hour PK sample. The subject will be instructed to return for the next treatment period or for the final follow-up visit, as appropriate. The final follow-up visit will occur 35 days after the last dose of study drug. Subjects will be assigned to each of the two treatments randomly as per the randomization schedule.
- Conditions
- Hypothyroidism
- Being tested
- Levothyroxine
- Medical subject headings
- Hypothyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevothyroxineDrug
Single dose of 600mcg of test formulation of levothyroxine administered in dosing period 1 or 2.
LevothyroxineDrug
Single dose of 600mcg of reference formulation of levothyroxine administered in dosing period 1 or 2.
| Study group | Role | What they receive |
|---|---|---|
| Test formulation of levothyroxine | Active comparator | Single dose of 600 mcg of levothyroxine administered in dosing period 1 or 2.. Receives: Drug: Levothyroxine |
| Reference formulation of levothyroxine | Active comparator | Single dose of 600 mcg of levothyroxine administered in dosing period 1 or 2. Receives: Drug: Levothyroxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: -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
Cmax of serum T4 and T3 without adjustment by baseline levels of endogenous T4.
Measured: -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)
AUC (0-48) of serum T4 and T3 without adjustment by baseline levels of endogenous T4.
Measured: -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
Tmax of serum T4 and T3 with and without adjustment by baseline levels of endogenous T4.
Measured: -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
Kel of serum T4 and T3 with and without adjustment by baseline levels of endogenous T4.
Measured: -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
t1/2 of serum T4 and T3 with and without adjustment by baseline levels of endogenous T4.
Measured: -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.
Serum TSH
Change in serum TSH
Measured: At 12 hours pre-dose and 48 hours post dose
Adverse events
Number of participants with adverse events
Measured: Up to 70 days after initiation of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2012 (estimated)
- Study startJan 2012
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypothyroidismStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01536678
- Sponsor's protocol ID
- 116526
- Status last verified
- Oct 2012
- First submitted
- 2 Feb 2012
- Last updated
- 11 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bioequivalence of Two Levothyroxine Tablet Formulations in Healthy Indian Volunteers: A Single-dose, Randomized, Open-label, Crossover Study
- ClinicalTrials.gov ID
- NCT01536678
- Acronym / sponsor ID
- 116526
- Conditions
- Hypothyroidism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 22 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Levothyroxine (T4) is used to treat patients with hypothyroidism and may often result in lifelong therapy. Its physiologically active metabolite is tri-iodothyronine (T3). Levothyroxine is also endogenously produced in the body. Since small changes in levothyroxine administration (e.g. change in brand or formulation) can cause significant changes in serum thyroid stimulating hormone (TSH) concentrations, precise and accurate TSH control is critical to avoid potential adverse iatrogenic effects. Till date, the active pharmaceutical ingredient (API) for levothyroxine tablets marketed in India has been sourced from company 1. GSK India proposes to change the source of the API from the existing source (company 1) to to new source (company 2). In view of this change in the source of API, it is essential to determine whether it has any impact on drug product performance based on pharmacokinetic (PK) measures of total serum T4 and total serum T3 of the to-be-marketed formulation of levothyroxine (test formulation from company 2, Treatment A) relative to the formulation currently in the market (reference formulation from company 1, Treatment B).
This will be a single-center, open-label, two-period, two-treatment, two-sequence, randomized, single-dose, crossover study. 26 healthy adult males will be randomized to receive a single dose (6 x 100mcg tablets = 600mcg) of the test formulation of levothyroxine and reference formulation of levothyroxine separately in each treatment period. There will be two treatment sequences (AB, BA) and a 35 day washout between the two treatment periods.
The study will be conducted at BA/BE facility after approval from an independent ethics committee. Subjects will have a screening visit within 21 days prior to the first dose of study drug, two treatment periods with each containing a single dose of study drug, followed by 48 hours of serial PK sample collection. Subjects will check out of the unit on Day 3 (at 7am) after collection of the 48 hour PK sample. The subject will be instructed to return for the next treatment period or for the final follow-up visit, as appropriate. The final follow-up visit will occur 35 days after the last dose of study drug. Subjects will be assigned to each of the two treatments randomly as per the randomization schedule.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Test formulation of levothyroxine | Active comparator | Drug: LevothyroxineSingle dose of 600 mcg of levothyroxine administered in dosing period 1 or 2.. |
| Reference formulation of levothyroxine | Active comparator | Drug: LevothyroxineSingle dose of 600 mcg of levothyroxine administered in dosing period 1 or 2. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (16 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevothyroxineSingle dose of 600mcg of test formulation of levothyroxine administered in dosing period 1 or 2. | Drug | Test formulation of levothyroxine |
| LevothyroxineSingle dose of 600mcg of reference formulation of levothyroxine administered in dosing period 1 or 2. | Drug | Reference formulation of levothyroxine |
Primary outcome
Maximum observed concentration (Cmax) and Area under concentration-time curve [AUC (0-48)]
Time frame: -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.
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.
7 secondary outcomes
Cmax
Time frame: -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)
Time frame: -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
Time frame: -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
Time frame: -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
Time frame: -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.
Serum TSH
Time frame: At 12 hours pre-dose and 48 hours post dose
Adverse events
Time frame: Up to 70 days after initiation of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2013.
Related trials for Hypothyroidism
Not yet recruitingObservational study
Validation of Uzbek SARC-F and IPAQ-SF Questionnaires in Adults With and Without Hypothyroidism
Hypothyroidism, Psychometrics
RecruitingObservational study
Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
Congenital Disorders of Glycosylation
Active, not recruitingPhase 4
Comparison of Two Timings of Levothyroxine Intake in Hypothyroid Patients: A Cross-over Randomized Control Trial
Hypothyroidism Primary
RecruitingObservational study
Understanding the Subnormal Rescue ofNeurological Development in Congenital Hypothyroidism (2022E5SZEM)
Congenital Hypothyroidism, Neurodevelopmental Disorders
RecruitingObservational study
Prevalence and Associated Factors of High BMI and Periodontitis in Thai Adults Aged Under 60 Years
Diabete Mellitus, Dyslipidaemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Levothyroxine in people with Hypothyroidism, run by GlaxoSmithKline at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum observed concentration (Cmax) and Area under concentration-time curve [AUC (0-48)] (time frame: -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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2013.