Autosomal dominant hypocalcaemia type 1 (ADH1) Nutritional, Metabolic, Endocrine
Conditions
Interventions
Participants will receive a single oral administration of 54 mg [14C]encaleret Oral Solution containing not more than (NMT) 3.7 megabecquerel (MBq) 14C in the fasted state.
Sponsors
Calcilytix Therapeutics, Inc., a BridgeBio Company
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. Must be willing to consume the drug dose, which contains a small amount of alcohol and is radiolabelled with 14C 4. Aged 40 to 65 years inclusive at the time of signing informed consent 5. Must agree to adhere to the contraception requirements defined in the clinical protocol 6. Healthy males as assessed by the investigator 7. Body mass index (BMI) of 18.0 to 35.0 kg/m² as measured at screening 8. Must have regular bowel movements (i.e. average stool production of =1 and =3 stools per day)
Exclusion criteria
Exclusion criteria: 1. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients 2. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active 3. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or GI disease (especially peptic ulceration, GI bleeding, ulcerative colitis, Crohn’s Disease or Irritable Bowel Syndrome), neurological or psychiatric disorder, as judged by the investigator 4. History of GI surgery (with the exception of appendectomy unless it was performed within the previous 12 months) 5. Acute diarrhoea or constipation in the 7 days before the predicted Day 1. If screening occurs >7 days before the Day 1, this criterion will be determined on Day 1. Diarrhoea will be defined as the passage of liquid faeces and/or a stool frequency of greater than 3 times per day. Constipation will be defined as a failure to open the bowels more frequently than every other day 6. Subject has a medical condition that may adversely affect taste or smell activity including but not limited to mouth ulcers, significant gum disease, and respiratory and/or sinus infection or cold 7. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 8. Evidence of current SARS-CoV-2 infection within 4 weeks of IMP administration 9. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert’s Syndrome are allowed 10. Subjects with corrected Ca above the upper limit of the normal reference range 11. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results 12. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of 21 units per wee
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Mass balance recovery of total radioactivity in all excreta (urine and faeces): CumAe and Cum%Ae. 2. Collection of plasma, urine and faeces samples for metabolite profiling, structural identification, and quantification analysis of encaleret metabolites. The timepoints will be evaluated from collection of urine and faeces from pre-dose on Day 1 until a maximum of 264 hours post-dose (Day 12) in the clinical unit, home collections may be required after this time. Plasma samples will be collected from Day 1 to Day 12. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Determination of routes and rates of elimination of [14C]encaleret by calculation of Ae, %Ae, CumAe and Cum%Ae for total radioactivity by interval in all excreta (urine and faeces). 2. Identification of the chemical structure of each metabolite accounting for more than 10% by area under the curve (AUC) of circulating total radioactivity or accounting for 10% or more of the administered radioactive dose in excreta (urine and faeces). Collection of urine and faeces from pre-dose on Day 1 until a maximum of 264 hours post-dose (Day 12) in the clinical unit, home collections may be required after this time. 3. PK parameters for encaleret, its metabolites, M1 and M3, and total radioactivity in plasma following a single oral dose of encaleret, including but not limited to the following as applicable: Tmax, Cmax, AUC(0-last), AUC(0-inf), T1/2 and metabolite ratios taken from pre-dose on Day 1 to 168 hours post-dose (Day 8) 4. Evaluation of whole blood: plasma concentration ratios for total radioactivity taken from pre-dose on Day 1 to 168 hours post-dose (Day 8) 5. To provide additional safety and tolerability information for encaleret by assessing incidence of AEs, physical examinations and change from baseline for vital signs, ECGs, and laboratory safety tests from screening to discharge (Day 12 maximum) | — |
Countries
England, United Kingdom
Contacts
Public ContactGustavo Lorente
Outcome results
None listed