Study Evaluating Subjects With Distal Renal Tubular Acidosis

NCT03644706 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: B23CS
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 8

Brief Summary

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

Conditions

Distal Renal Tubular Acidosis

Outcome Measures

Primary Outcomes (1)

• Mean change in blood bicarbonate levels

  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

  6 days

Study Arms (2)

ADV7103

ACTIVE COMPARATOR

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

Drug: ADV7103

Placebo Comparator

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

ADV7103 DRUG

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).

Also known as: Potassium Citrate and Potassium Bicarbonate

ADV7103

Placebo DRUG

Placebo is a combination of 2 mm green coated lactose granules and 2 mm white coated lactose granules to be taken by mouth. Each dose of placebo contains a fixed ratio of 1/3 of green granules and 2/3 of white granules.

Placebo Comparator

Eligibility Criteria

• Age: 6 Months - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male subjects ≥ 6 months of age and ≤ 65 years of age at time of consent;
• 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;
• Subject requires ≥ 0.9 mEq/kg/day of alkali therapy to maintain serum bicarbonate levels above the LLN for the laboratory providing results;
• Subject or parent/guardian is willing and able to understand and sign informed consent and willing to comply with protocol instructions; child assent when appropriate; and
• Heterosexually active female subjects of childbearing potential and non-sterilized males must use at least one of the following acceptable birth control methods from informed consent through 7 days after the last dose of study product:
• Double-barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository)
• Established use of oral, injectable, or implanted hormonal methods of contraception
• Placement of an intrauterine device or intrauterine system
• Abstinence Females of childbearing potential are those who have reached the onset of menarche (or 8 years of age, whichever comes first) and are not postmenopausal (≥ 1 year without menses prior to Visit 1), surgically sterile, or status post hysterectomy (≥ 1 month prior to Visit 1). From informed consent through 7 days after the last dose of study product, female subjects must agree to refrain from egg donation and male subjects must agree to refrain from sperm donation.

You may not qualify if:

• Female subject who is pregnant or lactating or has plans for pregnancy during the study;
• Subject has evidence of proximal tubule dysfunction (eg, hypophosphatemia, low serum uric acid, glycosuria, or amino aciduria);
• 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;
• 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;
• 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;
• Subject has any of the following laboratory abnormalities associated with Visit 1:
• AST and/or ALT \> 1.5x upper limit of normal (ULN)
• 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)
• Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 (according to the Modified Schwartz formula for children \[\<12years of age\] and Chronic Kidney Disease - Epidemiology Collaboration \[CKD-EPI\] equation for adolescents and adults \[≥12 years of age\])
• Total bilirubin \> ULN, except with known Gilbert's disease or in patients with dRTA and known hemolytic anemia due to a defect in SLC4A1.
• 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;
• In the opinion of the Investigator, the subject has a major medical or psychiatric condition (eg, significant cardiac disease, schizophrenia) or an unstable condition (eg, uncontrolled hypertension, asthma, diabetes, hypercholesterolemia, or cardiac disease) that would potentially interfere with the subject safely completing the study;
• In the opinion of the Investigator, the subject has a history of difficulty taking oral medication and/or conditions that may hinder absorption of the study drug (eg, any difficulty of swallowing, malabsorption, delayed gastric emptying, esophageal compression, intestinal obstruction, or other chronic gastrointestinal disease);
• Self-reported or parent/guardian reported alcohol abuse or drug abuse within the past 12 months;
• Subject is a solid organ or bone marrow transplant recipient;

Sponsors & Collaborators

• Advicenne Pharma: lead

Study Sites (8)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of South Florida Pediatric Infectious Disease

Tampa, Florida, 33606, United States

Location

Emory Children's Center

Atlanta, Georgia, 30322, United States

Location

J.W. Riley Hospital for Children/Indiana University

Indianapolis, Indiana, 46202, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Links

• Patient education
• Company website

MeSH Terms

Conditions

Acidosis, Renal Tubular

Interventions

Potassium Citrate; potassium bicarbonate

Condition Hierarchy (Ancestors)

Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Citric Acid; Citrates; Tricarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Laurence Greenbaum, MD, Ph.D.

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: August 23, 2018
• Study Start: September 20, 2021
• Primary Completion: December 20, 2023
• Study Completion: December 20, 2023
• Last Updated: March 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); CA (2)