Metformin versus Tolvaptan in adults with Autosomal Dominant Polycystic Kidney Disease (ADPKD): a phase 3a, independent, multi-centre, 2 parallel arms randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Bari Aldo Moro

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

8 Sep 2020 → ongoing

Decision date (initial)

2025-01-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AIFA

External identifiers

EU CT number

2024-517864-49-01

EudraCT number

2018-000477-77

ClinicalTrials.gov

NCT03764605

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

Primary objective of the study is to define if a two years course of 1500 mg a day of metformin is equivalent or not inferior to tolvaptan in reducing eGFR decline in patients affected by ADPKD

Secondary objectives 1

1. Secondary objectives are to define if Metformin tratment for ADPKD is safe and effective in reducing kidney volume enlargement and in reducing symptoms related to this pathology.

Conditions and MedDRA coding

Autosomal Dominant Polycystic Kidney Disease

Study design 2 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Men and women aged between 18 and 55 years
2. mean of eGFR (CKD-EPI) in SV1 and SV2 ≥ 45 ml/min/1,73 m2
3. Genetic Diagnosis of Type I ADPKD truncating mutation
4. Signed and dated informed consent

Exclusion criteria 14

1. Women of childbearing potential (WOCBP) who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of IMP. If employing birth control, 2 of the following precautions must be used: vasectomy of partner, tubal ligation, vaginal diaphragm, intrauterine device, condom, or sponge with spermicide. Non childbearing potential in women is defined as female subjects who are surgically sterile (ie, have undergone bilateral oophorectomy or hysterectomy) or female subjects who have been postmenopausal for at least 12 consecutive months.
2. Women who are breast-feeding and/or who have a positive pregnancy test result prior to receiving investigational medical product (IMP).
3. Treatment with acarbose, guar gum, cimetidin, phenprocoumon, oral anticoagulants, thrombolytic drugs, diuretics, ranolazin, cephalexin.
4. Evidence of active systemic or localized major infection at the time of screening.
5. Hepatic impairment or liver function abnormalities other than that expected for ADPKD with typical cystic liver disease during the screening period as defined by: AST or ALT >8x UNL; AST or ALT >5x UNL >2 WEEKS; AST or ALT >3x UNL and BT >2x UNL OR INR >1,5; AST or ALT >3x UNL and SIGNS AND SYMPTOMS OF LIVER DAMAGE (fatigue, anorexy, nausea, vomiting, right hypocondrium pain, fever, jaundice, skin rash, itching)
6. Acute or chronic disease causing tissue hypoxia (e.g.: myocardial failure, severe arythmias, myocardial infarction, respiratory failure, liver failure, alcohol acute intoxication, alcoholism, dehydration).
7. Previously diagnosed diabetes already in treatment with other hypoglycemic drugs.
8. Ongoing breast feeding.
9. Use of any other investigational drug or treatment up to 4 weeks before enrollment and during the treatment phase.
10. Known hypersensitivity to metformin and its derivatives.
11. Psychiatric disorders and any condition that might prevent full comprehension of the purposes and risks of the study.
12. Malignancies within three years before enrolment in the study.
13. HIV, HBV, HCV infection.
14. Urinary tract obstruction.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary outcome of the study is to evaluate the treatments difference (between Metformin and Tolvaptan) in annualized slope of eGFR (CKD-epi) for individual subjects will be calculated using an appropriate baseline and post-randomization assessment

Secondary endpoints 1

1. The key secondary endpoint is the percent change from baseline in htTKV as measured by CT-scan at 12 and 24 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Bari Aldo Moro

Sponsor organisation

University Of Bari Aldo Moro

Address

Piazzale Giulio Cesare 11

City

Bari

Postcode

70124

Country

Italy

Scientific contact point

Organisation

University Of Bari Aldo Moro

Contact name

Dipartimento di Medicina di Precisione e Rigenerativa e Area Jonica - DiMePRe-J

Public contact point

Organisation

University Of Bari Aldo Moro

Contact name

Dipartimento di Medicina di Precisione e Rigenerativa e Area Jonica - DiMePRe-J

Third parties 1

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications