Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD

• Status: Completed
• Trial end date: 2011-06-01
• Target enrollment: 0
• Participant gender: All

Summary

To establish pharmacokinetics (PK), pharmacodynamics (PD), and adverse event (AE) profile of tolvaptan administered as the modified-release (MR) formulation in ADPKD subjects. The goals of this trial are two-fold:

1. To directly compare the immediate release (IR) and MR formulations

2. To determine the dose range and dose regimen for MR (dose finding)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Treatments: Tolvaptan

Criteria

Inclusion Criteria:

• Subjects (male or female) who are surgically sterile (ie, have undergone hysterectomy) or using contraception or agree to remain abstinent

• Subjects between the ages of 18 and 50, inclusive

• Subjects with a body mass index between 19 to 35 kg/m2 (inclusive)

• Subjects with a diagnosis of ADPKD by modified Ravine criteria

• Subjects must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests

• Subjects with the ability to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principle investigator, to comply with all requirements of the trial

• Subjects who expect to be able to complete all dosing periods and assessments within 42 (+2) days after dosing on Day 1

Exclusion Criteria:

• Subjects using diuretics within 14 days prior to check in on Day -1

• Subjects with incontinence, overactive bladder, or urinary retention (eg, benign prostatic hyperplasia)

• Subjects (male or female) with nocturia/urgency (outside of the 2 to 4 times awakening per night expected for ADPKD patients) at screening

• Subjects with liver disease, liver function abnormalities or serology other than that expected for ADPKD with cystic liver disease at baseline

• Subjects with clinically significant abnormality in past medical history, or at the Screening physical examination, that in the investigator's or sponsor's opinion may place the volunteer at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of drug. This includes, but is not limited to, history of or concurrent cardiac, hepatic, renal, neurologic, endocrine, gastrointestinal, respiratory, hematologic, and immunologic disease

• Subjects with a history of drug and/or alcohol abuse within 2 years prior to screening

• Subjects who have a history of or test positive at screening for hepatitis B surface antigen (HBsAg), hepatitis C antibodies (anti-HCV), and/or human immunodeficiency virus (HIV)

• Subjects who have clinically significant allergic reactions to tolvaptan or chemically related structures such as benzazepines (eg, benzazepril, conivaptan, fenoldopam mesylate or mirtazapine)

• Subjects who have taken an investigational drug within 30 days preceding trial entry

• Subjects with any history of significant bleeding or hemorrhagic tendencies

• Subjects with a history of difficulty in donating blood

• Subjects who have donated blood or plasma within 30 days prior to dosing

• Subjects who have consumed alcohol and/or food or beverages containing methylxanthines, grapefruit, grapefruit juice, Seville oranges, or Seville orange juice within 72 hours prior to Day 1 dosing

• Subjects taking CYP3A4 inhibitors, with the exception of amiodarone, taken within 30 days of dosing (eg, amprenavir, atorvastatin, aprepitant, chloramphenicol [not eye drops], cimetidine, clarithromycin, clotrimazole [if used orally], danazol, delavirdine, diltiazem, erythromycin, fluconazole, fluvoxamine, indinavir, isoniazid, itraconazole, josamycin, ketoconazole, nelfinavir, nefazadone, quinupristin/dalfopristin, ritonavir, saquinavir, troleandomycin, verapamil)

• Subjects taking CYP3A4 inducers taken within 7 days of dosing (eg, rifampin, St. Johns Wort)

• Subjects with a history of serious mental disorders

• Subjects with previous exposure to tolvaptan