A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Participants With Hydroxyurea-Resistant/Intolerant Polycythemia Vera

Inclusion Criteria:

- Adults > 18 years of age

- Documentation that the participant has met the revised 2016 World Health Organization
(WHO) criteria for the diagnosis of polycythemia vera (PV)

- Hematocrit at screening and at initiation of idasanutlin > 40%

- Phlebotomy-dependent participants with splenomegaly by magnetic resonance imaging
(MRI) or computerized tomography (CT) imaging (≥ 450 cubic centimeters [cm^3]) or
without splenomegaly (< 450 cm^3, unpalpable, or prior splenectomy)

- Resistance to/intolerance to hydroxyurea according to modified European Leukemia Net
(ELN) criteria

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

- Participants must be willing to submit the blood sampling and bone marrow sampling for
the pharmacokinetic (PK) and pharmacodynamic analyses and exploratory biomarkers

- Adequate hepatic and renal function

- For women of childbearing potential: agreement to use contraceptive methods that
result in a failure rate of < 1% per year during the treatment period and for at least
6 weeks after the last dose of idasanutlin

- For men: Agreement to use contraceptive measures, and agreement to refrain from
donating sperm during the treatment period and for at least 90 days after the last
dose of idasanutlin

Exclusion Criteria:

- Meets the criteria for post-PV myelofibrosis as defined by the International Working
Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)

- Blast phase disease (>20% blasts in the marrow or peripheral blood)

- Clinically-significant thrombosis within 3 months of screening

- Participants who must receive CYP2C8 inhibitors, substrates and inducers, strong
CYP3A4 inducers, or OATP1B1/3 substrates while on study. These must be discontinued 7
days (inhibitors and substrates) or 14 days (inducers) prior to start of study
medication

- Participants previously treated with murine double minute 2 (MDM2) antagonist
therapies or participants receiving interferon-alpha, anagrelide, or ruxolitinib
within 28 days or 5 half-lives, or hydroxyurea within 1 day, or participants receiving
any other cytoreductive or investigational agents within 28 days or 5 half-lives of
initial dose. Aspirin is permitted per treatment guidelines for PV unless medically
contraindicated

- Participants with evidence of electrolyte imbalance such as hypokalemia, hyperkalemia,
hypocalcemia, hypercalcemia, hypomagnesemia, and hypermagnesemia of Grade > 1
intensity, as per the National Cancer Institute Common Terminology Criteria for
Adverse Events (NCI CTCAE), version 4.0, prior to dosing on Cycle 1 Day 1. Treatment
for correction of electrolyte imbalances is permitted to meet eligibility

- Neutrophil count < 1.5 × 10^9/liter (L) prior to dosing on Cycle 1 Day 1

- Platelet count ≤ 150 × 10^9/L prior to dosing on Cycle 1 Day 1

- Women who are pregnant or breastfeeding

- Ongoing serious non-healing wound, ulcer, or bone fracture

- History of major organ transplant

- Uncontrolled intercurrent illness including, but not limited to hepatitis, concurrent
malignancy that could affect compliance with the protocol or interpretation of
results, hepatitis A, B, and C, human immunodeficiency virus (HIV)-positive, ongoing
or active infection, clinically significant cardiac disease (New York Heart
Association Class III or IV), symptomatic congestive heart failure, unstable angina
pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements

- Participants with active gastrointestinal conditions (Crohn's disease, ulcerative
colitis, diverticulosis associated colitis, and Behçet's disease)

- Clinically significant toxicity (other than alopecia) from prior therapy that has not
resolved to Grade ≤ 1 (according to the NCI CTCAE, v4.0) prior to Cycle 1 Day 1