Plain English Summary
Background and study aims
Levothyroxine is a synthetic thyroid hormone that is normally used to substitute the natural hormone when the thyroid, for several reasons, does not produce this hormone at all or does not produce it in sufficient amounts. The absorption of levothyroxine is affected by the intake of food and the recommendation is to take it in the fasting state and wait between 30 min and 1 hour before having breakfast. Exactly how long one should wait before the meal and whether different formulations require different fasting times have not been investigated. The aim in this study is to compare the absorption profile of oral levothyroxine administered at a single dose in healthy volunteers at different times before breakfast.
Who can participate?
Women, aged 18–50 years old, who are generally healthy
What does the study involve?
Healthy volunteers will be randomly allocated to oral levothyroxine as a single dose (600 µg) at different times: they will take two or three single doses of levothyroxine in the fasting state or 15 minutes and/or 30 minutes before a light breakfast.
What are the possible benefits and risks of participating?
Levothyroxine is usually well tolerated, although, in the event of hyperdosing, symptoms may occur such as palpitations, alterations of the cardiac rhythm, increased heart rate frequency, muscular cramps, insomnia, diarrhoea, vomiting, nervousness, headache, sweating, weight decrease, tremors, alterations of the menstrual cycle or loss of hair. There are no direct benefits from the participation.
Where is the study run from?
Cross Research SA (Switzerland)
When is the study starting and how long is it expected to run for?
From January 2015 to September 2015
Who is funding the study?
IBSA Institut Biochimique SA (Switzerland)
Who is the main contact?
Mrs Claudia Scarsi
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
14CH/T412
Study information
Scientific title
Effect of food on levothyroxine absorption following a single oral dose of 600 µg in healthy women: an randomised open-label pilot study
Acronym
Study hypothesis
To verifiy the absorption of levothyroxine after meals.
On 30/06/2015 the following changes were made to the trial record:
1. The overall trial end date was changed from 30/05/2015 to 30/09/2015.
2. The target number of participants was changed from 30 to 40.
Ethics approval
Comitato Etico Cantonale (Switzerland), 20/01/2015 (amendment n. 2 21/04/2015), reference number: 2871
Study design
Randomised open-label three-way bioavailability pilot study in two parts
Primary study design
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Other
Trial type
Other
Patient information sheet
Condition
Oral levothyroxine
Intervention
Healthy volunteers were administered oral levothyroxine as a single dose (600 mcg):
1. In the fasting state
2. 15 minutes before a light breakfast
3. 30 minutes before a light breakfast
Intervention type
Drug
Phase
Not Applicable
Drug names
Levothyroxine
Primary outcome measure
Effect of food on levothyroxine sodium bioavailability by comparison of the rate (Cmax) and extent (AUC0-t) of absorption of serum levothyroxine after a single dose of 600 µg: measured over 24 hours after each single dose, by repeated blood sampling and analytical quantitation of the serum concentration of levothyroxine
Secondary outcome measures
Effect of food on the secondary levothyroxine pharmacokinetic parameters after a single dose of 600 µg: measured over 24 hours after each single dose, by repeated blood sampling and analytical quantitation of the serum concentration of levothyroxine
Overall trial start date
28/11/2014
Overall trial end date
08/11/2016
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Signed written informed consent before inclusion in the study
2. Age 18–50 years old
3. Body-mass index: 18.5–27 kg/m2
4. Vital signs: systolic blood pressure 100–139 mmHg, diastolic blood pressure 50–89 mmHg, heart rate 50–90 beats per minute, measured after 5 minutes at rest in the sitting position
5. Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and comply with the requirements of the entire study
6. Women of child-bearing potential must be using at least one of the following reliable methods of contraception and must continue up to 30 days after the last investigational medicinal product administration: 6.1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit
6.2. Non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit
6.3. Male sexual partner who agrees to use a male condom with spermicide
6.4. Sterile sexual partner
6.5. Non-child-bearing potential or in post-menopausal status for at least 1 year
7. All thyroid function tests within normal limits
Participant type
Healthy volunteer
Age group
Adult
Gender
Female
Target number of participants
40
Participant exclusion criteria
1. Electrocardiogram 12-leads (supine position): clinically significant abnormalities
2. Physical findings: clinically significant abnormal physical findings that could interfere with the objectives of the study
3. Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
4. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study
5. Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular (including active arrhythmia or history of arrhythmia, particularly atrial fibrillation), respiratory, skin, haematological, genitourinary or neurological diseases that may interfere with the aim of the study; history of endocrine abnormalities, particularly thyroid, hypophysis and hypothalamus dysfunction; autoimmune diseases such as Basedow-Graves and Hashimoto morbi; neoplasia
6. Medications, including over the counter drugs and herbal remedies for 2 weeks before the start of the study
7. Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study; the 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study
8. Blood donations for 3 months before this study
9. Drug, alcohol, caffeine, tobacco: history of drug, alcohol (more than one drink per day defined according to the USDA Dietary Guidelines 2010), caffeine (more than five cups of coffee or tea per day) or tobacco abuse (at least 10 cigarettes per day)
10. Positive drug test results at screening or day–1
11. Positive alcohol breath test at day –1
12. Abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study
13. Vegetarians
14. Positive or missing pregnancy test at screening or day–1
15. Pregnant or lactating women
Recruitment start date
26/01/2015
Recruitment end date
09/06/2015
Locations
Countries of recruitment
Switzerland
Trial participating centre
Cross Research SA
6894
Switzerland
Funders
Funder type
Industry
Funder name
IBSA Institut Biochimique SA (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal
IPD Sharing plan:
The datasets generated during and/or analysed during the current study are/will be available upon request from Claudia Scarsi (Claudia.scarsi@ibsa.ch)
Intention to publish date
08/11/2018
Participant level data
Available on request
Basic results (scientific)
Publication list