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Study Evaluating Subjects With Distal Renal Tubular Acidosis

Primary Purpose

Distal Renal Tubular Acidosis

Status
Not yet recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ADV7103
Placebo
Sponsored by
Advicenne Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Distal Renal Tubular Acidosis

Eligibility Criteria

6 Months - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 <3.0 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;

Sites / Locations

  • Children's Hospital Colorado
  • University of South Florida Pediatric Infectious Disease
  • Emory Children's Center
  • J.W. Riley Hospital for Children/Indiana University
  • Montefiore Medical Center
  • The Children's Hospital of Philadelphia
  • University of Alberta
  • The Hospital for Sick Children

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

ADV7103

Placebo Comparator

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
August 22, 2018
Last Updated
May 8, 2023
Sponsor
Advicenne Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT03644706
Brief Title
Study Evaluating Subjects With Distal Renal Tubular Acidosis
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Advicenne Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
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. A follow-up period up to four weeks on re-established therapy completes the trial. Subjects can elect to return to their previous standard of care regimen after completing the withdrawal period or will have the opportunity to subsequently enter an open-label extension study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Distal Renal Tubular Acidosis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ADV7103
Arm Type
Active Comparator
Arm Description
Patients continue to receive ADV7103 twice a day at their open label dose over 6 days
Arm Title
Placebo Comparator
Arm Type
Placebo Comparator
Arm Description
Patients receive matched placebo twice a day until they reach a bicarbonate level of 18mEq/L
Intervention Type
Drug
Intervention Name(s)
ADV7103
Other Intervention Name(s)
Potassium Citrate and Potassium Bicarbonate
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Mean change in blood bicarbonate levels
Description
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
Time Frame
6 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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; Subject has a history of malignancy within 5 years prior to Visit 1, except for localized skin or cervical carcinoma; or Subject is known to have allergy or intolerance to any ADV7103 or placebo constituents.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Robbie McCarthy
Phone
+1.484.595.5001
Email
robbiemccarthy@advicenne.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laurence Greenbaum, MD, Ph.D.
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of South Florida Pediatric Infectious Disease
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Emory Children's Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
J.W. Riley Hospital for Children/Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2R3
Country
Canada
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.arena2drtastudy.com/
Description
Patient information regarding the disease under study and protocol information
URL
https://www.kidney.org/atoz/content/dRTA
Description
Patient education
URL
http://advicenne.com/
Description
Company website

Learn more about this trial

Study Evaluating Subjects With Distal Renal Tubular Acidosis

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