Trial Outcomes & Findings for TCUPS- Tolvaptan Use in Cystinuria and Urolithiasis: A Pilot Study (NCT NCT02538016)

Results Overview

The primary outcome was urinary cystine supersaturation as measured by "cystine capacity". This proprietary test (Litholink Corp., Chicago IL) is reported as a value in mg/L above or below zero, with positive values indicating urine undersaturated with cystine, while negative values indicate that the urine is supersaturated with cystine. Four 24-hour urine samples were obtained during the study: one at baseline 3-6 days prior to the measurement, one on day 3-4 of the dosing period, one on day 7-8 of the dosing period, and one 3-6 days after the washout period. Each 24 hour urine sample was sent individually for analysis by Litholink Corp, which performs the cystine assays.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

4 participants

Primary outcome timeframe

23 days

Results posted on

2020-07-10

Participant Flow

Recruitment and Enrollment period was between August 2016 to December 2018. Subjects were recruited from our existing database of cystinuria patients, from new patients presenting during the research period, and via advertising through the International Cystinuria Foundation, Rare Kidney Stone Consortium, and social media.

Of 6 eligible and interested participants, 5 met inclusion criteria and were consented, and of these, 1 withdrew prior to travel to our hospital for drug administration.

Participant milestones

Participant milestones
Measure	Tolvaptan This was a single arm, unblinded study. All participants received half of the recommended dose (weight-dependent) on Days 1 through 4 and then the full recommended dose (weight-dependent) on Days 5 through 8 Example of Dosing Schedule by Weight: Participant Weight is between: 12.5 kg -37.49 kg Then their Dose on Days 1-4 = 7.5mg (.6mg/kg -.2mg/kg) Dose on Days 5-8 is doubled = 15mg (1.2mg/kg - .4mg/kg) Maximum dose administered was 60 mg.
Overall Study STARTED	4
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tolvaptan n=4 Participants This was a single arm, unblinded study. All participants received half of the recommended dose (weight-dependent) on Days 1 through 4 and then the full recommended dose (weight-dependent) on Days 5 through 8 Example of Dosing Schedule by Weight: Participant Weight is between: 12.5 kg -37.49 kg Then their Dose on Days 1-4 = 7.5mg (.6mg/kg -.2mg/kg) Dose on Days 5-8 is doubled = 15mg (1.2mg/kg - .4mg/kg) Maximum dose administered was 60 mg.
Age, Categorical <=18 years	2 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=4 Participants
Sex: Female, Male Female	2 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: 23 days

The primary outcome was urinary cystine supersaturation as measured by "cystine capacity". This proprietary test (Litholink Corp., Chicago IL) is reported as a value in mg/L above or below zero, with positive values indicating urine undersaturated with cystine, while negative values indicate that the urine is supersaturated with cystine. Four 24-hour urine samples were obtained during the study: one at baseline 3-6 days prior to the measurement, one on day 3-4 of the dosing period, one on day 7-8 of the dosing period, and one 3-6 days after the washout period. Each 24 hour urine sample was sent individually for analysis by Litholink Corp, which performs the cystine assays.

Outcome measures

Outcome measures
Measure	Tolvaptan n=4 Participants Tolvaptan.
Urinary Cystine Supersaturation (mg/L) at High Dose (Day7-8)	70 mg/L Interval -3.0 to 111.0

SECONDARY outcome

Timeframe: 11 days

Secondary outcomes included serum sodium and other electrolyte levels. Serum electrolytes for each subject before, during, and after tolvaptan treatment (Sodium/Potassium/Chloride in mmol/L).

Outcome measures

Outcome measures
Measure	Tolvaptan n=4 Participants Tolvaptan.
Urine Osmolality at High Dose (Day 8) Sodium	141 mmol/L Interval 139.0 to 142.0
Urine Osmolality at High Dose (Day 8) Potassium	4.05 mmol/L Interval 3.7 to 4.4
Urine Osmolality at High Dose (Day 8) Chloride	102 mmol/L Interval 101.0 to 103.0

Adverse Events

Tolvaptan

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Tolvaptan n=4 participants at risk Tolvaptan.
Investigations Severe Thirst	100.0% 4/4 • 2 weeks

Additional Information

Alyssia Venna

Boston Children's Hospital

Phone: 617-919-6352

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place