Purpose

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

Eligibility

Eligible Ages
Between 6 Months and 65 Years
Eligible Genders
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 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;

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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: 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.

Recruiting Locations

Montefiore Medical Center
Bronx, New York 10467
Contact:
Patricia Flynn, RN
718-655-1120
PFLYNN@montefiore.org

More Details

NCT ID
NCT03644706
Status
Recruiting
Sponsor
Advicenne Pharma

Study Contact

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.