Tolvaptan Extension Study in Participants With ADPKD (TEMPO 4/4)

Otsuka

Status and phase: Completed; Phase 3

Conditions: Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Treatments: Drug: Tolvaptan

Study type: Interventional

Funder types: Industry

Identifiers

NCT01214421

2010-018401-10 (EudraCT Number)

156-08-271

Details and patient eligibility

About

To demonstrate whether tolvaptan modifies ADPKD progression as measured by changes from Baseline (from Study 156-04-251) in total kidney volume (TKV) and renal function.

Enrollment: 1,083 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants who had successfully completed a Phase 1, 2, or 3 tolvaptan ADPKD or renal impairment study, with a confirmed diagnosis of ADPKD from prior studies [either 156-04-251 (NCT00428948) or 156-04-250 (NCT00413777), 156-06-260, 156-09-284 (NCT01336972), 156-09-285 (NCT01210560), and 156-09-290 (NCT01451827)].

Exclusion criteria

• Participants unable to provide written informed consent.
• Participants (men or women) would not adhere to the reproductive precautions as outlined in the Informed Consent Form.
• Participants (women only) with a positive urine pregnancy test.
• Participants who were pregnant or breast-feeding.
• Participants unable to take oral medications.
• Participants who had allergic reactions to tolvaptan or chemically related structures such as benzazepines (benzazepril, conivaptan, fenoldopam mesylate, or mirtazapine).
• Participants with disorders in thirst recognition or an inability to access fluids.
• Participants with critical electrolyte imbalances, as determined by the investigator
• Participants with or at risk of significant hypovolemia, as determined by investigator.
• Participants with significant anemia, as determined by investigator.
• Participants with a history of substance abuse (within the last 3 years).
• Participants who were taking other experimental (that is, non-marketed) therapies or were participating in another clinical drug or device study; participating in the off-drug follow-up period of another ADPKD trial with tolvaptan was permitted.
• Participants unable to complete magnetic resonance imaging (MRI) assessments (for example, participants with ferro-magnetic prostheses, aneurysm clips, severe claustrophobia).
• Participants who had taken a vasopressin antagonist (outside of previous participation in a tolvaptan study).
• Participants unable to comply with anti-hypertensive or other important medical therapy.
• Participants with advanced diabetes.
• Participants who were taking medications or had an illness that could confound endpoint assessments (including taking approved therapies for the purpose of affecting polycystic kidney disease [PKD] cysts).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1,083 participants in 1 patient group

Tolvaptan

Experimental group

Description:

Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 milligrams (mg) in the morning \[AM\]/15 mg in the evening \[PM\] titrated to 60 mg \[AM\]/30 mg \[PM\], then 90 mg \[AM\]/30 mg \[PM\] based on tolerability were given orally twice daily until the last participant originating from prior studies (either 156-04-251 or 156-04-250, 156-06-260, 156-09-284, 156-09-285, and 156-09-290) who was eligible for efficacy analysis completed the Month 24.

Treatment:

Drug: Tolvaptan