Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (ADPKD) (TEMPO3:4)

Otsuka

Status and phase: Completed; Phase 3

Conditions: Polycystic Kidney Disease, Autosomal Dominant

Treatments: Drug: Tolvaptan; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00428948

156-04-251

2006-002768-24 (EudraCT Number)

Details and patient eligibility

About

This study's purpose is to evaluate the long-term safety and efficacy of tolvaptan versus placebo in patients with ADPKD.

Full description

This study evaluated whether or not tolvaptan is potentially beneficial, while maintaining an adequate safety profile, by reducing the rate of total kidney volume increase, while impacting the onset, severity, and progression of other important consequences of ADPKD.

During the 3-week titration phase, tolvaptan or placebo was titrated in weekly intervals from lowest to highest tolerated levels given in split-dose regimens of 45/15 mg, 60/30 mg and 90/30 mg orally upon awakening and approximately 9 hours later. As soon as a subject could not tolerate a given dose, the titration phase was over and the maintenance phase began at the dose level tolerated. The maintenance phase lasted to Month 36. Subjects were able to titrate down at any point during the study. Subjects were able to titrate up during the maintenance phase with Medical Monitor approval.

Enrollment: 1,445 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Legal adult age and able to give Informed Consent.
• Adult subjects with a diagnosis of ADPKD. A diagnosis of ADPKD (age 18 or 20-50) required several cysts in each kidney (3 if by sonography, 5 if by CT or MRI) in those with a family history of ADPKD and 10 cysts (by any radiologic method) in each kidney and exclusion of other cystic kidney diseases if there was no family history.
• Willingness to comply with reproductive precautions, if female.
• Estimated creatinine clearance ≥ 60 mL/min. Estimated from serum creatinine during screening using Cockcroft-Gault with correction for gender and race, where possible.
• Rapidly progressive kidney growth (total volume ≥ 750 cc) by magnetic resonance imaging (MRI) at randomization.

Exclusion criteria

• Prior exposure to tolvaptan or other experimental PKD therapies.
• Currently taking medication for purpose of affecting PKD cysts.
• Women who are breast feeding and females of childbearing potential who are not using acceptable contraceptive methods.
• In the opinion of the study investigator or sponsor may present a safety risk or confound study objectives.
• Patients who are unlikely to adequately comply with study procedures.
• Patients having contraindications to MRI.
• Patients taking medications or having any illnesses likely to affect ADPKD outcomes.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,445 participants in 2 patient groups, including a placebo group

Tolvaptan

Experimental group

Description:

Participants received the highest tolerated split-dose regimen (upon awakening and 9 hours later) of tolvaptan 45/15 mg, 60/30 mg, or 90/30 mg orally for 36 months.

Treatment:

Drug: Tolvaptan

Placebo

Placebo Comparator group

Description:

Participants received placebo (upon awakening and 9 hours later) orally for 36 months.

Treatment:

Drug: Placebo