E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metabolic acidosis associated with Chronic Kidney Disease |
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E.1.1.1 | Medical condition in easily understood language |
Low blood bicarbonate levels in patients with chronic kidney disease (CKD) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027417 |
E.1.2 | Term | Metabolic acidosis |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and durability of effect of TRC101 in CKD patients with metabolic acidosis |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Have provided written informed consent prior to participation in the study. 2.Have completed the 12-week treatment period and attended the Week 12 Visit in the parent study TRCA-301. 3.Have a blood bicarbonate value of ≥ 12 mEq/L at the Week 12 Visit in Study TRCA-301, based on onsite measurement using the i-STAT point-of-care device. 4.Have adequate peripheral venous access for blood draws. 5.Women who are of childbearing potential must have negative pregnancy test at the Week 12 Visit and be willing to use an acceptable method of birth control until 1 month after study completion. Acceptable methods include hormonal contraception (oral contraceptives, patch, implant, and injection), intrauterine devices, double barrier methods (e.g., vaginal diaphragm, vaginal sponge, condom, spermicidal jelly), sexual abstinence or a vasectomized partner. Women who are surgically sterile with documentation of such, or who are at least 1-year post-last menstrual period and > 55 years of age, are considered not to be of childbearing potential.
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E.4 | Principal exclusion criteria |
1.Have any level of low blood bicarbonate at the Week 12 Visit that, in the opinion of the Investigator, requires emergency intervention or evaluation for an acute acidotic process. 2.Required dialysis for acute kidney injury or worsening CKD during the parent study TRCA-301. 3.Planned initiation of renal replacement therapy (dialysis or transplantation) within 6 months following study entry. 4.Have a history or current diagnosis of clinically significant diabetic gastroparesis (based on Investigator’s judgment) or a history of bariatric surgery. 5.Have a history or current diagnosis of bowel obstruction, swallowing disorders, severe gastrointestinal (GI) disorders, inflammatory bowel disease, major GI surgery, or active gastric/duodenal ulcers. 6.Have a serum calcium ≤ 8.0 mg/dL at the Week 10 Visit in the parent study, TRCA-301. 7.Have active cancer during the 1 year prior to the Week 12 Visit, other than non-melanoma skin cancer, or cancer that is currently being treated or will be treated during the study. Subjects with cancers that are being treated with hormonal therapy only may be permitted with approval of the Medical Monitor. 8.Inability to consume the study drug, known allergy to the study drug or otherwise comply with the protocol. 9.Have, in the opinion of the Investigator, any medical condition, uncontrolled systemic disease or serious concurrent illness that would significantly decrease study compliance or jeopardize the safety of the subject or affect the validity of the study results.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint: Incidence of AEs, SAEs, and AEs leading to withdrawal.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Endpoint: Until 2 weeks after the end of treatment (Week 52 Visit). |
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E.5.2 | Secondary end point(s) |
Secondary endpoint: 1.Having a change from baseline (CFB) in blood bicarbonate ≥ 4 mEq/L or having blood bicarbonate in the normal range (22 to 29 mEq/L) 2.CFB in blood bicarbonate 3.CFB in the total score of the Kidney Disease and Quality of Life (KDQOL) Question 3 items (daily activities) 4.CFB in repeated chair stand test duration
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoint: At the end of treatment (Week 52 Visit).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Croatia |
Georgia |
Hungary |
Serbia |
Slovenia |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 13 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 14 |