Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Multi-center, Double-blind, Placebo-controlled, Parallel-arm Trial to Determine Long-term Safety and Efficacy of Oral Tolvaptan Tablets Regimens in Adult Subjects With Autosomal Dominant Polycystic Kidney Disease
Brief Summary: This study's purpose is to evaluate the long-term safety and efficacy of tolvaptan versus placebo in patients with ADPKD.


Options:
A: Inclusion Criteria:

* Diagnosis of ADPKD.
* Age 15-49 (Study A); Age 18-64 (Study B).
* GFR \>60 mL/min/1.73 m2 (Study A); GFR 25-60 mL/min/1.73 m2 (Study B).
* BP ≥130/80 or receiving treatment for hypertension.
* Informed Consent.

Exclusion Criteria:

* Pregnant/intention to become pregnant in 4-6 yrs.
* Documented renal vascular disease.
* Spot urine albumin-to-creatinine ratio of \>0.5 (Study A) or ≥1.0 (Study B) and/or findings suggestive of kidney disease other than ADPKD.
* Diabetes requiring insulin or oral hypoglycemic agents / fasting serum glucose of \>126 mg/dl / random non-fasting glucose of \>200 mg/dl.
* Serum potassium \>5.5 milliequivalent (mEq) /L for participants currently on ACE-I or ARB; \>5.0 mEq/L for participants not currently on ACE-I or ARB.
* History of angioneurotic edema or other absolute contraindication for ACE-I or ARB. Intolerable cough associated with ACE-I is defined as a cough developing within six months of initiation of ACE-I in the absence of other causes and resolving upon discontinuation of the ACE-I.
* Indication (other than hypertension) for β-blocker or calcium channel blocker therapy (e.g. angina, past myocardial infarction, arrhythmia), unless approved by the site principal investigator. (PI may choose to accept an individual who is on only a small dose of one of these agents and would otherwise be eligible.)
* Systemic illness necessitating nonsteroidal antiinflammatory drugs (NSAIDs), immunosuppressant or immunomodulatory medications.
* Systemic illness with renal involvement.
* Hospitalized for acute illness in past 2 months.
* Life expectancy \<2 years.
* History of non-compliance.
* Unclipped cerebral aneurysm \>7mm diameter.
* Creatine supplements within 3 months of screening visit.
* Congenital absence of a kidney (also total nephrectomy for Study B).
* Known allergy to sorbitol or sodium polystyrene sulfonate.
* Exclusions specific to magnetic resonance (MR) imaging (Study A).
B: 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.
C: Inclusion Criteria:

* Male or female ADPKD patient between 18 and 40 years of age
* measured GFR higher than 70 ml/min 1.73m2
* documented kidney volume progression
* informed consent

Exclusion Criteria:

* Female of childbearing potential who is planning to become pregnant, who is pregnant and/or lactating, who is unwilling to use effective means of contraception
* increased liver enzymes (2-fold above normal values)
* hypercholesterolemia (fasting cholesterol \> 8 mmol/l) or hypertriglyceridaemia (\> 5 mmol/l) not controlled by lipid lowering therapy
* granulocytopenia (white blood cell \< 3,000/mm3) or thrombocytopenia (platelets \< 100,000/mm3),
* infection with hepatitis B or C, HIV
* any past or present malignancy
* mental illness that interfere with the patient ability to comply with the protocol
* drug or alcohol abuse within one year of baseline
* co-medication with strong inhibitor of CYP3A4 and or P-gp like voriconazole, ketoconazole, diltiazem, verapamil, erythromycin
* co-medication with strong CYP3A4 and or P-gp inductor like rifampicin
* known hypersensitivity to macrolides or Rapamune
D: Inclusion Criteria:

* ADPKD patients.
* Blood pressure measured at out-patient setting is above 130/85 mmHg.
* Age between 20 and 60 years old.
* Plasma creatinine less than 2.0mg in man and 1.5mg in woman.
* Patients give informed consent.

Exclusion Criteria:

* Patients with severe cardiovascular and hepatic disorders.
* Patients with complications of central nervous vascular disorders.
* Women who are breast feeding and females of childbearing potential who are not using acceptable contraceptive methods.
* Patients currently engaging in other experimental protocol.
* Patients with intracranial aneurysma.
* Patients who must use diuretics.
* Allergic patients to Candesartan or Cilnidipine.
* Patients whose hypertension is not controlled by medication of this protocol.

Answer: B