Hyperphosphatemia
Conditions
Interventions
Cohort 1: receiving AP306 75 mg, twice a day (BID), orally
Cohort 2:receiving AP306 125 mg, BID, orally
Cohort 3:receiving AP306 150 mg, BID, orally
Cohort 4:receiving AP306 75 mg, three times a day (TID), orally
Cohort 5:receiving AP306 100 mg, TID, orally
Cohort 6:receiving AP306 125 mg, TID, orally
Cohort 7:receiving the placebo of AP306, TID, orally
Sponsors
Peking University People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated ICF, stated willingness to comply with all study procedures and availability for the duration of the study 2. Male or female assigned at birth, age >=18 years at the time of signing the ICF 3. On a stable hemodialysis (including hemodialysis, hemodiafiltration, and hemoadsorption) regimen, which is defined at a frequency of three times per week for at least 12 weeks prior to signing the ICF and not planned to change throughout the study 4. Serum phosphate within the range, via Central Laboratory, as follows: ? For participants who are not receiving tenapanor or phosphate binders within 2 weeks prior to signing the ICF: a serum phosphate of >=6.0 mg/dL (1.94 mmol/L) but =4.5 mg/dL (1.45 mmol/L) but =6.0 mg/dL (1.94 mmol/L) but =1.20, (estimated with pre- and post-dialysis blood urea nitrogen (BUN)/urea), at screening, or any documented value >=1.20 within 12 weeks prior to signing the ICF 6. If the participant is receiving etelcalcetide, their doses must be unchanged for at least 4 weeks prior to signing the ICF. 7. If the participant is receiving any of the following therapies, their doses must be unchanged for at least 14 days prior to signing the ICF: ? Phosphate-lowering products other than tenapanor or phosphate binders, such as nicotinamide, cholestyramine, cuttlebone, and hydrotalcite ? Active vitamin D and analogs (such as paricalcitol, calcifediol, and doxercalciferol)Protocol AP306-HP-202, Version 4.0 30 ? Cinacalcet ? Calcitonin ? P-glycoprotein inhibitors or inducers (see Appendix 2) 8. For female of childbearing potential and non-sterile male who is sexually active with a female partner of childbearing potential: agreement to use highly effective contraception consisting of at least one method throughout the study and for 90 days after the final dose of the study drug, as defined below: A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (>=12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (such as Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. Acceptable contraceptive methods include bilateral tubal ligation, male sterilization, hormonal contraceptives, hormone-releasing intrauterine devices, copper intrauterine devices, male or female condoms with or without spermicide, and cap, diaphragm, or sponge with spermicide. Hormonal contraceptives (oral, parenteral, or transdermal) MUST be used at least 8 weeks prior to signing the ICF. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condoms and male condoms should not be used together.
Exclusion criteria
Exclusion criteria: 1. Pregnant or breastfeeding, or intending to become pregnant after signing the ICF or within 90 days after the final dose of the study drug Women of childbearing potential must have a negative serum pregnancy test at screening 2. Scheduled for a living donor kidney transplant in the next 6 months, planned change to peritoneal dialysis or home hemodialysis during the study; planned relocation to another dialysis center during the study 3. Any history of a non-pharmacological parathyroid intervention, such as surgical parathyroidectomy and percutaneous ethanol injection therapy, within 6 months prior to signing the ICF, or planned parathyroid intervention during the study 4. Total serum calcium 11.0 mg/dL (2.75 mmol/L) via Central Laboratory. 5. Serum iPTH >1000 pg/mL (106 pmol/L) via Central Laboratory 6. Hemoglobin 3× upper normal limit (ULN) at screening Protocol AP306-HP-202, Version 4.0 31 8. Any clinically significant GI disorders within 4 weeks prior to signing the ICF, including GI bleeding, bowel obstruction, dysphagia, colitis, inflammatory bowel disease, irritable bowel syndrome, gastro-duodenal ulcer, and uncontrolled chronic constipation or diarrhea; or any history of gastrectomy; or any GI tract surgery, excluding appendectomy and polypectomy, within 12 weeks prior to signing the ICF 9. Uncontrolled hypertension at screening, defined as pre-dialysis diastolic blood pressure (DBP) >110 mmHg or systolic blood pressure (SBP) >180 mmHg, or in the investigator’s opinion the participant’s hypertension is uncontrolled 10. Hospitalization for cardiac or cardiocerebrovascular disease within 24 weeks prior to signing the ICF 11. QT interval corrected with Fridericia’s formula (QTcF) >470 ms in females and >450 ms in males at screening, or any family history of congenital long QT syndrome or congenital arrhythmia 12. Any clinically significant active infection or infestation or any treatment with systemic anti-microbial treatment within 2 weeks prior to signing the ICF 13. History or presence of malignancy within 3 years prior to signing the ICF, except basal cell skin cancer, in-situ carcinoma of the cervix, and in-situ prostate cancer If the malignancy is considered cured and the life expectancy of the participant exceeds 1 year after the end of any cancer treatment, the participant can be enrolled. 14. Concomitant use of moderate or strong cytochrome P450 (CYP) 3A inhibitors within 2 weeks or 5 half-lives, whichever is longer, prior to signing the ICF (see Appendix 2)Topical use is allowed. 15. Treatment with any investigational medication or medical device within 30 days prior to signing the ICF 16. Life expectancy less than 12 months 17. In the investigator’s opinion, unsuitable to receive the study drug or undergo study testing procedures for any reason
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in serum phosphorus from baseline to the end of treatment, or before the initiation of rescue therapy, or before the interruption of study drug due to serum phosphorus < 2.5 mg/dL (0.81 mmol/L).; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) Characteristics;Proportion of Subjects Achieving Serum Phosphorus Levels Within the Target Range;Change in Serum Phosphorus from Baseline to End of Treatment;Time to Response of Serum Phosphorus Reduction;AEs, laboratory parameters, vital signs, ECG parameters, and the Bristol Stool Form Scale;Intact Parathyroid Hormone, Fibroblast Growth Factor 23; | — |
Countries
China
Contacts
Public ContactLi Zuo
Peking University People's Hospital
Outcome results
None listed