Health Condition 1: E211- Secondary hyperparathyroidism, notelsewhere classified
Conditions
Interventions
Intervention1: LNP1892: LNP1892 25 mg QD (PK PD study) for 8 days
LNP1892 10 mg QD (Main Study) for 90 days
LNP1892 25 mg QD (Main Study) for 90 days
Control Intervention1: Placebo: 10 mg QD (Main S
Sponsors
Lupin Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1) Ambulatory patients of either gender with >=18 years of age with diagnosis of SHPT associated with CKD, with Estimated Glomerular Filtration Rate (eGFR) 2) CKD (Stage 4 & 5) patients with SHPT, on Hemodialysis (or) Not on Hemodialysis and fulfilling additional criteria given below. CKD Patients not on Hemodialysis - 1. Patients with mean of 2 intact parathyroid hormone (iPTH) values obtained during the screening period >=110 pg/mL/ 12.1 pmol/L (CKD stage 4) or >=300 pg/mL/ 33 pmol/L (CKD stage 5) CKD Patients on Hemodialysis 1. Patients must be receiving maintenance hemodialysis 3 times weekly OR a minimum of 10 hemodialysis/ month for at least 3 months 2. Patients with mean of 2 intact parathyroid hormone (iPTH) values obtained during the screening period at least 300 pg/mL (33 pmol/L) and not greater than 1200 pg/mL (132 pmol/L) 3. Patients who have not used cinacalcet or are justified to shift from current cinacalcet use for any of the following reasons - 1 > Patients not tolerating cinacalcet: a. Nausea/ Vomiting b. Hypocalcemia (serum corrected calcium c. Paraesthesia d. Any other adverse events not tolerated by the patient 2 > Patients not responding to cinacalcet: a. Patients who fail to achieve PTH goal of b. Less than 30% reduction from baseline PTH levels after 3 months of treatment c. Patients with PTH more than 800 pg/ml while being on cinacalcet 3) Patients who are on stable doses of active vitamin D or vitamin D analogues/ sterols (e.g. calcitriol, alfacaidol, paricalitol, or doxercalciferol) and/or phosphate binders for at least 3 weeks prior to Day 1 4) Patients who are on stable doses of calcium supplements for at least 1 week prior to Day 1 5) Patients must not have taken cinacalcet within 21 days prior to Day 1 6) Patients with mean of 2 corrected total serum calcium values obtained during the screening period >=8.4 mg/dL (2.10 mmol/L) 7) Patients with hemoglobin >=8.0 g/dL 8) Patients with serum magnesium level above the lower limit of normal 9) Participants of reproductive potential (males and females), must be willing to use a reliable means of contraception (combined or progesterone only hormonal contraception, intrauterine devices, surgical sterilization, double barrier methods, or vasectomized partner) throughout trial participation and 3 month after the last dose of IP; OR Women if postmenopausal (aged greater than 45 years) must have a history of amenorrhea for at least 1 year from the time of last menstrual cycle and have follicle stimulating hormone (FSH) value indicating menopause with high reliability. 10) Patient is in stable condition and has life expectancy of at least 6 months in the judgement of the investigator
Exclusion criteria
Exclusion criteria: 1. History of Primary hyperparathyroidism 2. Subject has known sensitivity to any of the products or components to be administered during dosing. 3. Anticipated or scheduled kidney transplant during the study period. 4. Parathyroidectomy within 3 months prior to screening or parathyroid surgery is planned or anticipated during the study 5. Change in dialysate calcium concentration in the 30 days prior to Day 1 6. Patients on peritoneal dialysis 7. History of symptomatic ventricular dysrhythmias or torsades de pointes, uncontrolled hypertension, symptoms of angina pectoris at rest or minimal activity, congestive heart failure (New York Heart Association Class III or IV ), history of myocardial infarction, coronary angioplasty, coronary arterial bypass grafting within 6 months prior to screening 8. Treatment of a seizure disorder or history of seizure in the last 12 months prior to screening. 9. Participation in another investigational trial in the past 1 month prior to screening. 10. Women who are pregnant, lactating, or planning pregnancy while enrolled in the study and at least 3 month after last dose of the IP 11. History of any immunosuppressive or biologic response modifiers therapy within 6 months prior to screening 12. History of abuse of alcohol or recreational drugs within 1 year prior to screening 13. Tested seropositive for Hepatitis B [Hepatitis B surface antigen (HBsAg)], and Hepatitis C virus (HCV), or human immunodeficiency virus (HIV) 14. Have any known condition affecting oral absorption of drug e.g., (malabsorption syndrome), or not able to swallow IP for any reason 15. Patient has current or recent history of a severe, progressive, or uncontrolled disease or an unstable medical condition (apart from disease under investigation) based on medical history, physical examination or any clinically significant laboratory/investigation findings, which in the opinion of investigator makes the patient inappropriate for inclusion in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean percentage change in iPTHTimepoint: 90 days | — |
Secondary
| Measure | Time frame |
|---|---|
| 110 pg/mL or less for those with stage 4 CKDTimepoint: 90 days;300 pg/mL or less for those with stage 5 CKDTimepoint: 90 days;Exploratory Endpoints. For Efficacy. 1. Change from baseline in parathyroid gland size For PD. 1. Mean absolute change and mean percent change from baseline in calcitonin and FGF23 levels Timepoint: 90 days;PD. Mean absolute change and mean percent change from baseline in corrected total serum calcium and phosphorusTimepoint: 90 days;PK(single dose and steady-state kinetics). Maximum concentration (Cmax), time to maximum concentration (tmax), area under the curve (AUC0-last, AUC0-inf, AUC0-24h), half-life (t1/2), apparent clearance (CL/F), apparent volume of distribution (Vz/F)Timepoint: 90 days;Proportion of patients with â?¥30% reduction in iPTHTimepoint: 90 days;Safety. 1. Adverse Event Assessment 2. Physical Examinations 3. Vital Signs 4. Clinical Safety Laboratory tests (hematology, biochemistry and urinalysis) 5. ECGsTimepoint: 90 days | — |
Countries
India, United Kingdom
Contacts
Public ContactDr Amit Joshi
Lupin Limited
Outcome results
None listed