Monocarboxylate Transporter 8 (MCT8) deficiency also known as Allan Herndon Dudley Syndrome (AHDS) Not Applicable
Conditions
Interventions
Each participant will receive a single oral dose of each of treatments A and B, and three other treatments (i.e. 5 of the 6 treatments in total) on one occasion across five study periods with a minimu
Sponsors
Rare Thyroid Therapeutics International AB
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Must provide written informed consent 2. Must be willing and able to communicate and participate in the whole study 3. Aged 18 to 55 years inclusive at the time of signing informed consent 4. Must agree to adhere to the contraception requirements 5. Healthy males 6. Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening 7. Weight 50 to 100 kg at screening
Exclusion criteria
Exclusion criteria: 1. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients, including lactose or galactose intolerance 2. Presence or history of any malabsorption of galactose or glucose 3. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active 4. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or GI disease, neurological or psychiatric disorder, or surgical procedure or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, as judged by the investigator 5. Acute illness, surgical procedures, or trauma from within 14 days before screening (i.e. signing the ICF) until first administration of IMP, as judged by the investigator 6. History of active malignancy or neoplastic disease in the previous 12 months 7. Presence of a suspected/manifested clinically significant acute or chronic infection, as judged by the investigator 8. History of human immunodeficiency virus infection (HIV), hepatitis B, or hepatitis C; history of positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody, or hepatitis C virus antibody (HCV Ab) 9. Subjects with a history of cholecystectomy or gallstones 10. Planned inpatient surgery, dental procedure, or hospitalisation during the study 11. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 12. Any clinically significant abnormalities in physical examination, as judged by the investigator 13. Clinically significant abnormal clinical chemistry, haematology, or urinalysis as judged by the investigator. Note: Subjects with Gilbert’s Syndrome are not allowed 14. Values outside the normal reference range for any of the following safety laboratory analytes: serum TSH, T3, T4, FT4, total cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, ferritin, parathyroid hormone (PTH) or sex hormone binding globulin (SHBG,) if judged by the investigator to be clinically significant at the screening visit 15. Positive HBsAg, HCV Ab or HIV 1 and 2 antibody results at screening 16. Evidence of renal impairment at screening, as indicated by an estimated glomerular filtration rate (eGFR) of 140 mmHg, supine diastolic blood pressure >90 mmHg, or heart rate =35 or =100 beats per minute), as judged by the investigator at screening or pre dose of Period 1 18. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, as judged by the investigator at screening or pre dose of Period 1 19. Subjects who have received any IMP in a clinical research study within the 90 days prior to Period 1 Day 1, or less than 5 elimination half-lives prior to Period 1 Day 1, whichever is longer 20. Donation of blood or plasma within the previous 1 month or loss of greater than 400 mL of blood within the previous 3 months 21. Subjects who are taking, or have taken, any prescribed or over-the-counter drug (including anticoagulants), vitamins, dietary supplements or herbal remedies (other than up to 4 g of paracetamol per day)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PK parameters Cmax, AUC(0-last) and AUC(0-inf) for tiratricol in serum measured using blood samples at pre-dose and multiple timepoints up to 72 h post-dose | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. PK parameters, including (but not limited to): Cmax, AUC(0-last), AUC(0-inf) Tmax, T1/2, CL/F and Vz/F for tiratricol in serum, and concentration vs time profiles for serum (triiodothyronine) T3 and (thyroxine) T4 measured using blood samples at pre-dose and multiple timepoints up to 72 h post-dose 2. Incidence of adverse events (AEs), physical examinations and change from baseline for vital signs, electrocardiograms (ECGs), and laboratory safety tests (including free thyroxine [FT4], T4 and thyroid-stimulating hormone [TSH]), from the time of signing the informed consent form up until the follow-up visit (5 to 7 days post-final dose) | — |
Countries
England, United Kingdom
Contacts
Public ContactMarie Bengtson
Outcome results
None listed