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Study Evaluating Subjects With Distal Renal Tubular Acidosis

Sponsor
Advicenne Pharma (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT03644706
Collaborator
(none)
40
Enrollment
12
Locations
2
Arms
14
Anticipated Duration (Months)
3.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 3, prospective, multicenter, randomized, double-blinded, placebo-controlled, study product withdrawal study comparing the efficacy of ADV7103 versus placebo in preventing the development of metabolic acidosis defined by serum bicarbonate level in pediatric (6 months to < 18 years of age) and adult (18 to 65 years of age) subjects with primary dRTA.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

The study will target enrolling at least 4 subjects in each of the following age groups: 6 months - 23 months; 2-11 years, and ≥ 12 years. Subjects will be in the study for up to 21 weeks. After screening and enrollment, subjects will participate in an 8-12 week open label period where there dose of ADV7103 will be titrated to effect, then continued for the remainder of the open label period. Periodic measurements of bicarbonate and potassium levels will be collected during this period. Following the open-label period, subjects will enter a 6-day randomized withdrawal period. For this portion of the study, subjects will be admitted to an inpatient setting. A follow-up period up to four weeks on re-established therapy completes the trial. Subjects will have the opportunity to subsequently enter a long-term, open label extension.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Phase 3 Multicenter, Randomized, Double-Blinded, Placebo-Controlled Withdrawal Study Evaluating ADV7103 In Pediatric and Adult Subjects With Distal Renal Tubular Acidosis (dRTA)
Anticipated Study Start Date :
Jun 1, 2021
Anticipated Primary Completion Date :
Apr 1, 2022
Anticipated Study Completion Date :
Aug 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: ADV7103

Patients continue to receive ADV7103 twice a day at their open label dose over 6 days

Drug: ADV7103
Each dose of ADV7103 contains a fixed ratio of 1/3 of ADV7103-CK (potassium citrate) and 2/3 of ADV7103-BK (potassium bicarbonate) based on the mass of active substances. The strength is 6.44 (± 10 %) mEq/g of ADV7103 (alkalinizing power).
Other Names:
  • Potassium Citrate and Potassium Bicarbonate

    		•
    Placebo Comparator: Placebo Comparator

    Patients receive matched placebo twice a day until they reach a bicarbonate level of 18mEq/L

    Drug: Placebo
    Placebo is a combination of 2 mm green coated lactose granules and 2 mm white coated lactose granules. Each dose of placebo contains a fixed ratio of 1/3 of green granules and 2/3 of white granules.

    Outcome Measures

    Primary Outcome Measures

    1. Mean change in blood bicarbonate levels [6 days]

      Compare the efficacy of ADV7103 versus placebo in preventing metabolic acidosis, defined as 2 consecutive serum bicarbonate levels < 18 mEq/L for subjects ≥ 4 years old and < 17 mEq/L for subjects < 4 years old, during the Withdrawal Period

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Months to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Female or male subjects ≥ 6 months of age and ≤ 65 years of age at time of consent;

    2. Subject presents with a previous diagnosis of primary dRTA of at least 4 months duration for subjects < 12 years of age, and at least one year for those ≥ 12 years of age, based on documented history of non-anion gap, hyperchloremic, hypokalemic metabolic acidosis;

    3. Subject requires ≥ 0.9 mEq/kg/day of alkali therapy to maintain serum bicarbonate levels above the LLN for the laboratory providing results;

    Exclusion Criteria:

    1. Female subject who is pregnant or lactating or has plans for pregnancy during the study;

    2. Subject has evidence of proximal tubule dysfunction (eg, hypophosphatemia, low serum uric acid, glycosuria, or amino aciduria);

    3. Subject presents with another diagnosed condition as a potential etiology for her/his dRTA (eg, systemic lupus erythematosus, Sjogren's syndrome), in the opinion of the Investigator;

    4. Subject requires therapy with potassium sparing diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, trimethoprim, drospirenone and other progestins, nephrotoxic antibiotics, penicillins, tacrolimus, or medications known to delay gastric emptying or otherwise interfere with absorption of study product;

    5. Subject has evidence of obstructive uropathy or other findings on renal ultrasound associated with Visit 1 expected to require intervention during the course of the study, in the opinion of the Investigator;

    6. Subject has any of the following laboratory abnormalities associated with Visit 1:

    7. AST and/or ALT > 1.5x upper limit of normal (ULN)

    8. Serum potassium > 5.0 mEq/L or <3.0 mEq/L or hypokalemia accompanied by clinical symptoms (eg, muscle cramps) or significant ECG changes (eg T wave depression, U wave elevation)

    9. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (according to the updated Schwartz formula for children and Chronic Kidney Disease - Epidemiology Collaboration [CKD-EPI] formula for adults)

    10. Total bilirubin > ULN, except with known Gilbert's disease.

    11. Subject has been hospitalized or had outpatient surgery (other than minor skin and dRTA disease-related procedures or ear tube placement) in the past 6 months or is planning surgery in the next 6 months;

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California San Francisco California United States 94158
    2 Children's Hospital Colorado Aurora Colorado United States 80045
    3 Connecticut Children's Hospital Hartford Connecticut United States 06106
    4 University of South Florida Pediatric Infectious Disease Tampa Florida United States 33606
    5 Emory Children's Center Atlanta Georgia United States 30322
    6 J.W. Riley Hospital for Children Indianapolis Indiana United States 46202
    7 Washington University/St. Louis Children's Hospital Saint Louis Missouri United States 63110
    8 Montefiore Medical Center Bronx New York United States 10467
    9 The Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    10 University of Alberta Edmonton Alberta Canada T6G 2R3
    11 The Hospital for Sick Children Toronto Ontario Canada M5G 1X8
    12 The Research Institute of the McGill University Health Centre Montreal Quebec Canada H4A 3J1

    Sponsors and Collaborators

    • Advicenne Pharma

    Investigators

    • Study Chair: Andre Ulmann, MD, Ph.D., Advicenne Pharma

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Advicenne Pharma
    ClinicalTrials.gov Identifier:
    NCT03644706
    Other Study ID Numbers:
    • B23CS
    First Posted:
    Aug 23, 2018
    Last Update Posted:
    Jun 21, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Acidosis, Renal Tubular
    Acidosis
    Potassium Citrate

    Study Results

    No Results Posted as of Jun 21, 2021