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Study Evaluating Subjects With Distal Renal Tubular Acidosis

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ClinicalTrials.gov Identifier: NCT03644706
Recruitment Status : Recruiting
First Posted : August 23, 2018
Last Update Posted : October 7, 2019
Sponsor:
Information provided by (Responsible Party):
Advicenne Pharma

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
Distal Renal Tubular Acidosis Drug: ADV7103 Drug: Placebos 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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)
Actual Study Start Date : January 31, 2019
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : February 1, 2021


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 Name: 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: Placebos

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.





Primary Outcome Measures :
  1. Mean change in blood bicarbonate levels [ Time Frame: 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



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Ages Eligible for Study:   6 Months to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

    1. AST and/or ALT > 1.5x upper limit of normal (ULN)
    2. Serum potassium > 5.0 mEq/L or hypokalemia accompanied by clinical symptoms (eg, muscle cramps) or significant ECG changes (eg T wave depression, U wave elevation)
    3. 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)
    4. Total bilirubin > ULN, except with known Gilbert's disease.
  7. 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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03644706


Locations
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United States, California
University of California Not yet recruiting
San Francisco, California, United States, 94158
Contact: Daniel Schrader    415-476-9657    daniel.schrader@ucsf.edu   
Principal Investigator: Farzana Perwad, MD         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Kathleen Peoples    720-777-4708    Kathleen.peoples@childrenscolorado.org   
Principal Investigator: Bradley Dixon, MD         
United States, Connecticut
Connecticut Children's Recruiting
Hartford, Connecticut, United States, 06106
Contact: Krystal Perez    860-837-6359    KPerez02@connecticutchildrens.org   
Principal Investigator: Cynthia Silva, MD         
United States, Florida
University of South Florida Pediatric Infectious Disease Recruiting
Tampa, Florida, United States, 33606
Contact: Denise Casey, RN    813-259-8674    dcasey1@health.usf.edu   
Principal Investigator: Valerie Panzarino, MD         
United States, Georgia
Emory Children's Center Recruiting
Atlanta, Georgia, United States, 30322
Contact: Christy Kang    404-712-9998    christy.kang@emory.edu   
Principal Investigator: Laurence Greenbaum, MD         
United States, Indiana
J.W. Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Sherry Wilson    317-274-2576    slw2@iu.edu   
Principal Investigator: Amy Wilson, MD         
United States, Missouri
Washington University/St. Louis Children's Hospital Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Leslie Walther, RN, BSN    314-747-1349    leslie.walther@wustl.edu   
Principal Investigator: Kevin Barton, MD         
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Patricia Flynn, RN    718-655-1120    PFLYNN@montefiore.org   
Principal Investigator: Kimberly Reidy, MD         
United States, Pennsylvania
The Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Taylor Moatz    267-425-3937    moatzt@email.chop.edu   
Principal Investigator: Benjamin Laskin, MD         
Canada, Alberta
University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2R3
Contact: Dory Sample    780-248-5599    Dory.Sample@albertahealthservices.ca   
Principal Investigator: R. Todd Alexander, MD         
Canada, Ontario
The Hospital for Sick Children Not yet recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Natasha Jawa    416-813-7654    natasha.jawa@sickkids.ca   
Principal Investigator: Damien Noone, MD         
Sponsors and Collaborators
Advicenne Pharma
Investigators
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Study Director: Linda Law, MD Advicenne Pharma

Additional Information:
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Responsible Party: Advicenne Pharma
ClinicalTrials.gov Identifier: NCT03644706     History of Changes
Other Study ID Numbers: B23CS
First Posted: August 23, 2018    Key Record Dates
Last Update Posted: October 7, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Acidosis, Renal Tubular
Acidosis
Acid-Base Imbalance
Metabolic Diseases
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Potassium Citrate
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Expectorants
Respiratory System Agents