• Patient’s scheduled to have a MRI and a CT of the cervical spine within six months of each other in the Neuroradiology practice as medically indicated; or using outside CT exam if on EHR and within six months of MRI.  Adding research ZTE sequence to MRI scan.
• Patient's scheduled to have MRI and conventional angiogram post aneursym ablation as medically indicated, adding reserach ZTE sequence to MRI scan.
• Patients scheduled to have MRI of head for temporal bone assessment pre or post cochlear implant.
• Patients scheduled for MRI of C-Spine with or without Head for assessment of migraine trigger.
• Patients scheduled for MRI of Venous Stenting assessment.

• ---

  Exclusion Criteria:
• Any patient with metal hardware present in their cervical spine that interferes with greater than two vertebrae, pacermaker or other device implanted.   Those with aneursym clips, coils, stents may be enrolled if item is MRI conditional safe for scanning.
• Those who have devices not compatible or safe for MRI of 7 Tesla strength.
• Patient will be exclude if they cervical spinal surgery between exams.

• Male or female subjects between 28 days and < 12 weeks of age, inclusive.
• Must have clinical and imaging features that are consistent with a diagnosis of ARPKD with all the following characteristics:
  • Nephromegaly (> 2 standard deviations from age appropriate standard via ultrasound);
  • Multiple renal cysts;
  • History of oligohydramnios or anhydramnios.
• Ability for parent or guardian to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.

• Premature birth (≤ 32 weeks gestational age).
• Anuria or RRT.
• Evidence of syndromic conditions associated with renal cysts (other than ARPKD).
• Abnormal liver function tests including ALT and AST, > 1.2 × ULN.
• Parents with renal cystic disease.
• Need for chronic diuretic use.
• Cannot be monitored for fluid balance.
• Critical electrolyte imbalances, as determined by the investigator.
• Has or at risk of having significant hypovolemia as determined by investigator.
• Clinically significant anemia, as determined by investigator.
• Severe systolic dysfunction defined as ejection fraction < 14%.
• Serum sodium levels < 130 mmol/L.
• Cannot be taking any other experimental medications.
• Require ventilator support.
• Taking medications known to induce CYP3A4.
• Having an infection including viral that would require therapy disruptive to IMP dosing.
• Platelet count < 50,000 µL.

1. Aged 18 to 65 years
2. Ability to be enrolled within 12 hours of qualifying injury
3. Must have at least one uninjured upper or lower extremity  
4. Must have a “severe leg injury” meeting one of the following anatomical locations and mechanisms of injury.

1. Application of NIRS monitoring would be an impediment to care
2. Known prior injury, surgery, or disease of the lower extremity (including thigh) that alters normal circulation in the leg (including peripheral vascular disease)
3. Admission for atraumatic medical reasons (i.e. myocardial infarction, sepsis)
4. Consent cannot be obtained from the patient or their LAR within 12 hours of injury
5. Has already undergone fasciotomy of the injured leg prior to enrollment
6. Has spinal injuries that result in complete loss of function (complete spinal cord injuries)
7. Has bilateral upper and lower extremity injuries greater than simple soft tissue injuries
8. Is in police custody at presentation to the hospital
9. Is a woman who is pregnant
10. Has open injury on the injured leg that is large enough that at least two NIRS sensor cannot be safely placed.  At a minimum two sensors must be placed on the injured leg(s).

• Consented adult patients taking daily opioids at the time of admission to the Pain Rehabilitation Center will be included
• Consented adult patients here for opioid tapering therapy
• Patients with or without pre-existing history of RLS/WED can be enrolled

• Research authorization not provided
• Pediatric patients (<18 years of age) and patients who are unable to provide consent or have significant language barrier (limiting understanding of the questionnaire) will be excluded from the study

PRIOR TO STEP 1 REGISTRATION

• Pathologically proven diagnosis of adenocarcinoma of prostate cancer within 180 days prior to registration.
• High-risk disease defined as having at least one or more of the following:
  • PSA > 20 ng/mL prior to starting ADT;
  • cT3a-T4 by digital exam or imaging (American Joint Committee on Cancer [AJCC] 8th edition [Ed.]);
  • Gleason score of 8-10;
  • Node positive by conventional imaging with a short axis of at least 1.0 cm;
  • Appropriate stage for study entry based on the following diagnostic workup:
    • History/physical examination within 120 days prior to registration;
    • Bone imaging within 120 days prior to registration;
      • Note: To be eligible, patient must have no definitive evidence of bone metastases (M0) on bone scan or sodium fluoride (NaF) PET within 120 days prior to registration (negative Na F PET/CT or negative axumin or choline PET or negative fluciclovine, choline or prostate-specific membrane antigen (PSMA) PET within 120 days prior to registration is an acceptable substitute if they have been performed).
  • Patients who have bone metastases established only fluciclovine, choline, or PSMA PET but not definitive on bone scan or Na F PET will still be eligible.
  • CT or MRI of the pelvis within 120 days prior to registration (negative fluciclovine, choline, or PSMA PET within 120 days prior to registration is an acceptable substitute). As with bone staging, nodal staging for trial purposes will be based off of conventional imaging findings only.
  • Patients with confirmed N1 metastases on conventional imaging (CT/MRI) as defined by > 10 mm on short axis are eligible but will be automatically assigned to the intensification study. Patients who are positive by fluciclovine, choline, or PSMA PET (i.e., N1), but whose nodes do not meet traditional size criteria for positivity (i.e., they measure ≤ 10 mm on either the CT or MRI portion of the PET or on a dedicated CT or MRI) will not be considered N1 for the trial and will not automatically be assigned to the intensification study.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration.
  • Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration).
  • Platelet count ≥ 100,000 x 10^9/uL independent of transfusion and/or growth factors (within 120 days prior to registration).
  • Creatinine clearance (CrCl) ≥ 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration).
  • For Black patients whose renal function is not considered adequate by Cockcroft-Gault formula, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) may be used for calculating creatinine clearance for trial eligibility.
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) within 120 days prior to registration.
    • Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject is eligible.
    • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional ULN (within 120 days prior to registration).
    • Serum albumin ≥ 3.0 g/dL (within 120 days prior to registration).
• The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (didanosine [DDI] is not permitted) with undetectable viral load within 6 months are eligible for this trial and have a CD4 count ≥ 200 cells/microliter within 60 days prior to registration. Note: HIV testing is not required for eligibility for this protocol. Of note, for patients with HIV in the intensification trial randomized to abiraterone acetate and apalutamide, highly active antiretroviral therapy (HAART) may need to be adjusted to medications that do not interact with abiraterone acetate and apalutamide.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable after or on suppressive therapy within 60 days prior to registration, if indicated.
  • Note: HBV viral testing is not required for eligibility for this protocol.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the principal investigator.
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.

PRIOR TO STEP 2 RANDOMIZATION

• Confirmation of Decipher score.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 60 days prior. Note: Apalutamide may interfere with HCV drugs.
• Patients on HCV medications should alert their infectious diseases physician if they get randomized to apalutamide due to the possibility that apalutamide can affect the bioavailability of some HCV medications. HCV viral testing is not required for eligibility for this protocol.

For patients entering the Intensification Cohort ONLY:

• Patients must discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to Step 2 randomization.

For patients entering the Intensification Cohort ONLY:

• Serum potassium ≥ 3.5 mmol/L prior to Step 2 randomization.

PRIOR TO STEP 1 REGISTRATION

• Definitive radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e., bone scan, CT scan, MRI).
• Prior systemic chemotherapy within ≤ 3 years prior to registration; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration.
• Prior radical prostatectomy.
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
• Current use of 5-alpha reductase inhibitor.
  • Note: If the alpha reductase inhibitor is stopped prior to randomization the patient is eligible.
• Didanosine (DDI) antiretroviral therapy is not permitted.
• History of any of the following:
  • Seizure disorder;
  • Current severe or unstable angina;
  • New York Heart Association Functional Classification III/IV;
    • Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.
  • History of any condition that in the opinion of the investigator, would preclude participation in this study.
• Evidence of any of the following at registration:
  • Active uncontrolled infection requiring IV antibiotics;
  • Baseline moderate and severe hepatic impairment (Child-Pugh class B & C);
  • Inability to swallow oral pills;
  • Any current condition that in the opinion of the investigator, would preclude participation in this study.
• Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both luteinizing hormone-releasing hormone [LHRH] agonist and oral anti-androgen) is ≤ 60 days prior to registration; Please note: baseline PSA and testosterone must be obtained prior to the start of any ADT.

PRIOR TO STEP 2 RANDOMIZATION

• Evidence of known gastrointestinal disorder affecting absorption of oral medications at registration.

For patients entering the Intensification Cohort ONLY:

• Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily.

For patients entering the Intensification Cohort ONLY:

• Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] ≥ 160 mmHg or diastolic BP ≥ 100 mmHg);
• Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment.

PRIOR TO STEP 1 REGISTRATION

• Pathologically proven diagnosis of adenocarcinoma of prostate cancer within 180 days prior to registration.
• High-risk disease defined as having at least one or more of the following:
  • PSA > 20 ng/mL prior to starting ADT;
  • cT3a-T4 by digital exam or imaging (American Joint Committee on Cancer [AJCC] 8th edition [Ed.]);
  • Gleason score of 8-10;
  • Node positive by conventional imaging with a short axis of at least 1.0 cm;
  • Appropriate stage for study entry based on the following diagnostic workup:
    • History/physical examination within 120 days prior to registration;
    • Bone imaging within 120 days prior to registration;
      • Note: To be eligible, patient must have no definitive evidence of bone metastases (M0) on bone scan or sodium fluoride (NaF) PET within 120 days prior to registration (negative Na F PET/CT or negative axumin or choline PET or negative fluciclovine, choline or prostate-specific membrane antigen (PSMA) PET within 120 days prior to registration is an acceptable substitute if they have been performed).
  • Patients who have bone metastases established only fluciclovine, choline, or PSMA PET but not definitive on bone scan or Na F PET will still be eligible.
  • CT or MRI of the pelvis within 120 days prior to registration (negative fluciclovine, choline, or PSMA PET within 120 days prior to registration is an acceptable substitute). As with bone staging, nodal staging for trial purposes will be based off of conventional imaging findings only.
  • Patients with confirmed N1 metastases on conventional imaging (CT/MRI) as defined by > 10 mm on short axis are eligible but will be automatically assigned to the intensification study. Patients who are positive by fluciclovine, choline, or PSMA PET (i.e., N1), but whose nodes do not meet traditional size criteria for positivity (i.e., they measure ≤ 10 mm on either the CT or MRI portion of the PET or on a dedicated CT or MRI) will not be considered N1 for the trial and will not automatically be assigned to the intensification study.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration.
  • Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration).
  • Platelet count ≥ 100,000 x 10^9/uL independent of transfusion and/or growth factors (within 120 days prior to registration).
  • Creatinine clearance (CrCl) ≥ 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration).
  • For Black patients whose renal function is not considered adequate by Cockcroft-Gault formula, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) may be used for calculating creatinine clearance for trial eligibility.
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) within 120 days prior to registration.
    • Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject is eligible.
    • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional ULN (within 120 days prior to registration).
    • Serum albumin ≥ 3.0 g/dL (within 120 days prior to registration).
• The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (didanosine [DDI] is not permitted) with undetectable viral load within 6 months are eligible for this trial and have a CD4 count ≥ 200 cells/microliter within 60 days prior to registration. Note: HIV testing is not required for eligibility for this protocol. Of note, for patients with HIV in the intensification trial randomized to abiraterone acetate and apalutamide, highly active antiretroviral therapy (HAART) may need to be adjusted to medications that do not interact with abiraterone acetate and apalutamide.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable after or on suppressive therapy within 60 days prior to registration, if indicated.
  • Note: HBV viral testing is not required for eligibility for this protocol.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the principal investigator.
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.

PRIOR TO STEP 2 RANDOMIZATION

• Confirmation of Decipher score.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 60 days prior. Note: Apalutamide may interfere with HCV drugs.
• Patients on HCV medications should alert their infectious diseases physician if they get randomized to apalutamide due to the possibility that apalutamide can affect the bioavailability of some HCV medications. HCV viral testing is not required for eligibility for this protocol.

For patients entering the Intensification Cohort ONLY:

• Patients must discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to Step 2 randomization.

For patients entering the Intensification Cohort ONLY:

• Serum potassium ≥ 3.5 mmol/L prior to Step 2 randomization.

PRIOR TO STEP 1 REGISTRATION

• Definitive radiologic evidence of metastatic disease outside of the pelvic nodes (M1a, M1b or M1c) on conventional imaging (i.e., bone scan, CT scan, MRI).
• Prior systemic chemotherapy within ≤ 3 years prior to registration; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration.
• Prior radical prostatectomy.
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
• Current use of 5-alpha reductase inhibitor.
  • Note: If the alpha reductase inhibitor is stopped prior to randomization the patient is eligible.
• Didanosine (DDI) antiretroviral therapy is not permitted.
• History of any of the following:
  • Seizure disorder;
  • Current severe or unstable angina;
  • New York Heart Association Functional Classification III/IV;
    • Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.
  • History of any condition that in the opinion of the investigator, would preclude participation in this study.
• Evidence of any of the following at registration:
  • Active uncontrolled infection requiring IV antibiotics;
  • Baseline moderate and severe hepatic impairment (Child-Pugh class B & C);
  • Inability to swallow oral pills;
  • Any current condition that in the opinion of the investigator, would preclude participation in this study.
• Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both luteinizing hormone-releasing hormone [LHRH] agonist and oral anti-androgen) is ≤ 60 days prior to registration; Please note: baseline PSA and testosterone must be obtained prior to the start of any ADT.

PRIOR TO STEP 2 RANDOMIZATION

• Evidence of known gastrointestinal disorder affecting absorption of oral medications at registration.

For patients entering the Intensification Cohort ONLY:

• Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily.

For patients entering the Intensification Cohort ONLY:

• Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] ≥ 160 mmHg or diastolic BP ≥ 100 mmHg);
• Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment.

• Age ≥ 18 years old.
• Histologically or cytologically confirmed diagnosis of unresectable Stage III or metastatic (Stage IV) melanoma, including metastatic ocular melanoma, with estimated largest tumor diameter ≤ 5cm and ≤ 2 tumors ≥ 3 to ≤ 5 cm diameter.
• Cutaneous melanoma patients only:
  • At least one prior FDA approved systemic therapy in the metastatic setting; and disease progression after immune checkpoint inhibitors.
  • If tumor is BRAF-mutated, previous BRAF- and/or MEK-targeted therapies are required.
    • NOTE:  For ocular melanoma patients no current standard of care exists, so patients are permitted to be treated in1st line setting.
• Measurable disease by any imaging modality as defined by RECIST (version 1.1).
  • NOTE: Disease that is measurable by physical examination only is not eligible.
• Injectable disease (i.e., suitable for direct injection or through the use of ultrasound guidance) defined as:
  • At least 1 injectable and safely accessible cutaneous, subcutaneous, or nodal melanoma lesion ≥5 mm in longest diameter for metastatic cutaneous or mucosal melanoma;
  • At least one safely accessible liver metastasis for patients with metastatic ocular melanoma.
• Patients with metastatic ocular melanoma must meet all of the additional inclusion criteria:
  • No more than 25% overall tumor involvement of the liver by MRI imaging;
  • Child Pugh Score A;
  • Absence of ascites;
  • No portal vein thrombosis.
• Have resolution of all previous treatment-related toxicities to Grade 1 severity or lower.
• The following laboratory values obtained ≤ 14 days prior to registration:
  • Absolute neutrophil count (ANC) ≥ 1500/mm^3;
  • Platelet count ≥ 100,000/mm^3;
  • Hemoglobin ≥ 9.0 g/dL (without need for hematopoietic growth factor or transfusion support);
  • Alanine aminotransferase (ALT) ≤ 2.5 x ULN;
  • Aspartate transaminase (AST) ≤ 2.5 x ULN;
  • Total bilirubin ≤ 1.5 x ULN;
  • PT ≤ 1.5 x ULN (or international normalization ratio [INR] ≤ 1.4) or PTT/aPTT ≤ULN;
  • Serum creatinine within institutional limits of normal (≤ ULN).
• Life expectancy of ≥ 12 weeks.
• ECOG Performance Status (PS) 0 or 1.
• Willing and have the ability to comply with scheduled visits (including geographical proximity), treatment plans, laboratory tests, and other study procedures.
• Willing to provide all biological specimens as required by the protocol.
• Including fresh tissue for biomarker analysis (metastatic melanoma cohort with accessible injectable lesions only).
  • NOTE: Patients with cutaneous melanoma and accessible cutaneous/ subcutaneous lesions will have one lesion biopsied prior to the subject receiving the first dose of study treatment on Day 1 of Cycle 1 and the biopsy will be repeated on the injected target lesion and an uninjected lesion where possible post-virus treatment on Day 3.
  • NOTE: Repeat samples may be required if adequate tissue is not obtained.
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.
  • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Willing to use an adequate method of contraception (see Appendix III) from the first dose of study medication through 120 days after the last dose of study medication, for persons of childbearing potential or persons able to father a child only.

• Known standard therapy for the patient’s disease that is potentially curative or definitely capable of extending life expectancy.
• Any of the following prior therapies:
  • Prior chemotherapy ≤ 2 weeks prior to registration;
  • Prior immunotherapy (monoclonal antibodies) ≤ 3 weeks prior to registration;
  • Prior experimental agent ≤ 2 weeks prior to registration;
  • Prior radiation therapy ≤ 2 weeks prior to registration.
• Need for concurrent chemotherapy, immunotherapy, radiotherapy, ablation therapy or any ancillary therapy considered investigational (used for a non-FDA approved indication or in the context of a research investigation).
• Minor surgical or interventional procedure ≤ 7 days prior to registration.
• Major surgical procedure ≤ 21 days prior to registration.
• History or evidence of melanoma associated with immunodeficiency states (e.g., hereditary immune deficiency, organ transplant, or leukemia, requires concomitant treatment with immunosuppressive agents, including CTLA-4 agonists, or chronic oral or systemic steroid medication including physiological replacement doses for adrenal insufficiency.
• History of or plan for splenectomy or splenic irradiation.
• History or evidence of central nervous system (CNS) metastases.
• Active skin lesions (open wounds, severe rash, herpetic lesions, etc.).
• Prior non-oncology vaccine therapies used for the prevention of infectious disease ≤ 28 days prior to registration.
• Requires concomitant treatment with therapeutic anticoagulants.
• Known history of active tuberculosis.
• Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Known acute or chronic hepatitis B or hepatitis C infection (requires negative test).
• Metastatic ocular melanoma patients only: liver radioembolization ≤ 90 days prior to registration.
• No other active second malignancy other than non-melanoma skin cancers and in situ cervical cancers within 35 years of registration.
  • NOTE: A second malignancy is not considered active if all treatment for that malignancy is completed and the patient has been disease-free for at least 3 years prior to registration.
• No uncontrolled intercurrent illness including, but not limited to:
  • ongoing or active infection;
  • symptomatic congestive heart failure;
  • unstable angina pectoris;
  • uncontrolled symptomatic cardiac arrhythmia;
  • uncontrolled hypertension (defined as blood pressure >160/90).
• New York Heart Association classification III or IV, known symptomatic coronary artery disease or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias.
• Active CNS disorder or seizure disorder or known CNS disease or neurologic symptomatology.
• Pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of study treatment.
• Person of childbearing potential who is unwilling to use two (2) highly effective methods of contraception during study treatment and through 120 days after the last dose of study treatment.
• Person able to father a child who is unwilling to use a highly effective method of contraception during study treatment and through 120 days after the last dose of study treatment.