Tolvaptan-Octreotide LAR Combination in ADPKD

• Register: ClinicalTrials.gov
• Last refreshed on: 14 November 2022
• Main ID: NCT03541447
• Date of registration: 17/05/2018
• Prospective Registration: Yes
• Primary sponsor: Mario Negri Institute for Pharmacological Research
• Public title: Tolvaptan-Octreotide LAR Combination in ADPKD TOOL
• Scientific title: A Pilot, Phase II Study With a Prospective, Randomized, Cross-Over, Placebo-Controlled, Double-Blind Design to Assess the Short-Term Effects of Tolvaptan Plus Placebo vs Tolvaptan Plus Octreotide LAR Combination Therapy in ADPKD Patients With Normal Kidney Function or Hyperfiltration
• Date of first enrolment: December 12, 2018
• Target sample size: 20
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03541447
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Italy

Contacts

• Name: Giuseppe Remuzzi, MD
• Affiliation: CRC per le Malattie Rare Aldo e Cele Daccò

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Adult (>18-yr-old) men and women, with a clinical and ultrasonographic diagnosis of
ADPKD;

2. Serum creatinine < 1.0 mg/dl (for man) and < 1.2 mg/dl (for woman) and changes in
serum creatinine (and creatinine clearance when available) <30% over the last six
months;

3. Creatinine clearance > 80 ml/min/1.73m2 measured one to two weeks apart during the
pre-screening period;

4. GFR = 80 ml/min/1.73m2 (by iohexol plasma clearance technique) at screening and
baseline evaluations;

5. TKV ranging between 1000 and 2000 ml at screening (by ultrasound imaging) and at
baseline (by MRI) evaluations;

6. Female participants must be of non-childbearing potential or must agree to abstinence
or use a highly effective form of contraception;

7. Written informed consent.

Exclusion Criteria:

1. Patients with concomitant systemic, renal parenchymal or urinary tract disease;

2. Diabetes;

3. Overt proteinuria (urinary protein excretion rate >1 g/24 hours);

4. Abnormal urinalysis suggestive of concomitant, clinically significant glomerular
disease, urinary tract lithiasis, infection or obstruction, biliary tract lithiasis or
obstruction;

5. Hemorrhagic or complicated cysts which might acutely affect kidney function and
volumes;

6. QT-related ECG abnormalities;

7. Cancer and major systemic diseases that could prevent completion of the planned
follow-up or interfere with data collection or interpretation;

8. Hypersensitivity to the IMP active substance or to any of the excipients or to
benzazepine or benzazepine derivatives;

9. Concomitant treatment with drugs that may affect glomerular hemodynamics during the
three months before the beginning of the study (including ACE inhibitors, angiotensin
receptor blockers, aldosterone antagonists and non-steroideal anti-inflammatory
medications);

10. Elevated liver enzymes and/or signs or symptoms of liver injury prior to initiation of
treatment that meet the requirements for permanent discontinuation of tolvaptan

11. Patients with anuria, volume depletion and hypernatraemia

12. Patients who cannot perceive or respond to thirst

13. Ferro-magnetic prosthesis, aneurysm clips, severe claustrophobia or any other
contraindication to MRI evaluation;

14. Psychiatric disorders and any condition that could prevent full comprehension of the
purposes and risks of the study;

15. Pregnant or lactating;

16. Participation in another interventional clinical trial within the 4 weeks prior to
screening.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Autosomal Dominant Polycystic Kidney Disease

Intervention(s)

Drug: Octreotide LAR

Drug: Tolvaptan

Other: Placebo

Primary Outcome(s)

Glomerular Filtration Rate (GFR) [Time Frame: Changes from 4 weeks before randomization at baseline, 1,4,8,9,12 and 16 weeks after the randomization.]

Secondary Outcome(s)

Total Kidney Volume (TKV) [Time Frame: Changes from baseline at 4,8,12 and 16 weeks after the randomization.]

Secondary ID(s)

2017-004701-40

TOOL

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Otsuka Pharmaceutical Italy S.r.l.