anthonyyazdaniml/CT-ADE-SOC huggingface dataset:
Intervention: Ranolazine
Trial phase: Phase 3
ATC code: C01EB18
SMILES: COc1ccccc1OCC(O)CN1CCN(CC(=O)Nc2c(C)cccc2C)CC1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 11
Group description: Ranolazine: ranolazine 1000 mg PO BID for 3 months
Eligibility criteria:
Inclusion criteria:

World Health Organization (WHO) Group 1 PAH, defined as a pulmonary hypertension with mean pulmonary artery pressure > 25 mmHg, pulmonary capillary wedge pressure < 15 mmHg, and pulmonary vascular resistance > 3 Wood units.
Right ventricular dysfunction, defined as RV fractional area change < 32% or RV tricuspid annular plane systolic excursion (TAPSE) < 15 mm.
Symptoms of angina or angina equivalent (exertional dyspnea, exertional epigastric pain, exertional nausea).
New York Heart Association functional class II or III symptoms.
Stable doses of pulmonary vasodilators (prostacyclins, endothelin receptor antagonists, phosphodiesterase inhibitors), with no new therapy initiation or dose escalation > 50% in the 4 weeks prior to randomization.
Age 18-80 years.

Exclusion criteria:

Acute coronary syndrome or coronary revascularization within the prior 3 months.
Patients with unstable angina.
Patients with Class IV congestive heart failure.
Planned revascularization, pacemaker or defibrillator placement during the study period.
Changes in antianginal medical therapy likely to occur during the study period.
Corrected QT interval measurement >500 ms.
Patients with pre-existing QT prolongation (including congenital long QT syndrome) or receiving other QT prolonging drugs (including Class Ia-e.g., quinidine, Class III-e.g., dofetilide, sotalol, antiarrhythmics; antipsychotics (e.g., thioridazine, ziprasidone), or known history of complex ventricular arrhythmias requiring antiarrhythmic medications or ICD implantation.
Patients with known history of hepatic dysfunction.
Current use of strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir and diltizaem.
Patients with pacemakers, cochlear implants, aneurysm clips, who have worked with metal.
Patients with metallic hardware, implants, or prostheses will consult with the radiologist/cardiologist prior to the study.
Patients with severe or end stage renal disease (an estimated GFR < 30 mL/min/1.73 m).
Women who are pregnant or lactating

Any contraindications for the use of a right heart catheter including, but not limited to:

Pulmonic or tricuspid valve stenosis
Prosthetic pulmonic or tricuspid valve
Right atrial or ventricular masses
Previous pneumonectomy
Risk of severe arrhythmias, including left bundle branch block (LBBB)
Subjects unable to perform cardiopulmonary exercise testing will be excluded (i.e. extensive musculoskeletal disease)
Intervention: Risperidone
Trial phase: Phase 2
ATC code: N05AX08
SMILES: Cc1nc2n(c(=O)c1CCN1CCC(c3noc4cc(F)ccc34)CC1)CCCC2
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 36
Group description: Participants received risperidone tablet-in-capsule, dose was titrated with a starting dose of 1 mg up to 3 mg, orally every 12 hours for 28 days.
Eligibility criteria:
Inclusion Criteria:

Diagnosis of schizophrenia with acute exacerbation of illness
The current acute exacerbation of schizophrenia must be less than 4 weeks duration prior to the initial evaluation.

Exclusion Criteria:

Subjects with evidence or history of clinically significant uncontrolled medical illness
Subjects with a current diagnosis of schizoaffective disorder, major depression, bipolar disorder, or obsessive compulsive disorder.
Subjects who meet Diagnostic and Statistical Manual-IV (DSM-IV)defined diagnostic criteria for psychoactive substance dependence (excluding nicotine dependence) within 12 months of screening or DSM-IV defined substance abuse within 3 months prior to screening.
Intervention: Vapendavir
Trial phase: Phase 2
SMILES: CCOc1noc2cc(OCCC3CCN(c4ccc(C)nn4)CC3)ccc12
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 154
Group description: BTA798: BTA798 twice daily
Eligibility criteria:
Inclusion Criteria:

Male and female subjects aged 18-70 years
Diagnosis of asthma consistent with Global Initiative for Asthma (GINA) steps 1 to 3
Presumptive human rhinovirus infection

Exclusion Criteria:

Current severe asthma exacerbation
Severe asthma, GINA steps 4 or higher
Uncontrolled or clinically significant medical condition, disease or event which could impact subject safety and/or study evaluations and/or compliance to the protocol
Current smoker, ex-smoker of <1 year, or history of smoking >/=10 pack years.
Intervention: Besifloxacin Hydrochloride
Trial phase: Phase 3
SMILES: Cl.NC1CCCCN(c2c(F)cc3c(=O)c(C(=O)O)cn(C4CC4)c3c2Cl)C1
Sex: All
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 518
Group description: besifloxacin ophthalmic suspension 0.6%

Besivance : Ocular administration to affected eye for 7 days
Eligibility criteria:
Inclusion Criteria:

Subjects must have a clinical diagnosis of acute bacterial conjunctivitis and exhibit purulent conjunctival discharge (crusty or sticky eyelids) and redness in at least one eye.
Subjects who are willing to discontinue contact lens wear for the duration of the study.
Subjects who are able and willing to comply with all treatment and follow- up/study procedures.

Exclusion Criteria:

Subjects who have any uncontrolled systemic disease or debilitating disease.
Subjects with a known hypersensitivity or contraindications to Besivance, fluoroquinolones, or any of the ingredients in the study drugs.
Subjects who are expected to require disallowed concurrent systemic or ocular therapy(either eye)during or prior to study start. (ie, NSAIDs, corticosteroids, mast cell stabilizers, antihistamines, decongestants or antimicrobial therapy)
Subjects having ocular surgery (including laser surgery) in either eye within six weeks prior to entry into this study.
Subjects with suspected viral or allergic conjunctivitis or any other disease conditions that could interfere with the efficacy and safety evaluations of the study medication.
Subjects with suspected iritis.
Subjects with a history of recurrent corneal erosion syndrome, either idiopathic or secondary to previous corneal trauma or dry eye syndrome.
Subjects with any active ulcerative keratitis, specifically any epithelial loss greater than punctate keratitis.
Subjects who are immune compromised.
Intervention: Daptomycin
Trial phase: Phase 4
ATC code: J01XX09
SMILES: CCCCCCCCCC(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(N)=O)C(=O)NC(CC(=O)O)C(=O)NC1C(=O)NCC(=O)NC(CCCN)C(=O)NC(CC(=O)O)C(=O)NC(C)C(=O)NC(CC(=O)O)C(=O)NCC(=O)NC(CO)C(=O)NC(C(C)CC(=O)O)C(=O)NC(CC(=O)c2ccccc2N)C(=O)OC1C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 40
Group description: 500 milligrams (mg) daptomycin, administered intravenously (IV) for 7 to 10 days accordingly to the package insert or according to institutional practice, if warranted.
Eligibility criteria:
Inclusion Criteria:

Complicated skin or skin structure infection (cSSSI)
Intravenous vancomycin home infusion ordered for 7-14 days

Exclusion Criteria:

Pregnant or lactating female
Concurrently receiving other systemic antibiotics with gram positive activity
Known or suspected allergy or hypersensitivity to daptomycin or vancomycin
Known or suspected vancomycin-resistant enterococci (VRE)
Known or suspected osteomyelitis, pneumonia, bacteremia, endocarditis, or urinary tract infection
Known or suspected human immunodeficiency virus (HIV), cancer, or autoimmune disease such as lupus
Receiving systemic concomitant immunosuppressive agents such as chemotherapy, corticosteroids, tacrolimus, sirolimus, or cyclosporine, during the duration of the study
Requirement for non-study gram positive systemic antibiotics
Known to be allergic or intolerant to intravenous vancomycin or daptomycin
Participants with known or suspected creatinine clearance (CLcr) < 30 milliliters per minute (mL/min)
In skilled nursing facility
In hospice or admission to hospice is planned
Intervention: Vancomycin
Trial phase: Phase 4
ATC code: A07AA09 | J01XA01 | S01AA28
SMILES: CN[C@H](CC(C)C)C(=O)N[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H]2C(=O)N[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)O)c4cc(O)cc(O)c4-c4cc3ccc4O)[C@H](O)c3ccc(c(Cl)c3)Oc3cc2cc(c3O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O[C@H]2C[C@](C)(N)[C@H](O)[C@H](C)O2)Oc2ccc(cc2Cl)[C@H]1O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 40
Group description: Vancomycin monotherapy is administered according to prescribing physician's order with duration of treatment modified, if warranted, according to Investigator site's standard practice, and End of Treatment (EOT) is dependent on this. Dose adjustments of vancomycin will be suggested by the pharmacist and approved by prescribing or following physician.
Eligibility criteria:
Inclusion Criteria:

Complicated skin or skin structure infection (cSSSI)
Intravenous vancomycin home infusion ordered for 7-14 days

Exclusion Criteria:

Pregnant or lactating female
Concurrently receiving other systemic antibiotics with gram positive activity
Known or suspected allergy or hypersensitivity to daptomycin or vancomycin
Known or suspected vancomycin-resistant enterococci (VRE)
Known or suspected osteomyelitis, pneumonia, bacteremia, endocarditis, or urinary tract infection
Known or suspected human immunodeficiency virus (HIV), cancer, or autoimmune disease such as lupus
Receiving systemic concomitant immunosuppressive agents such as chemotherapy, corticosteroids, tacrolimus, sirolimus, or cyclosporine, during the duration of the study
Requirement for non-study gram positive systemic antibiotics
Known to be allergic or intolerant to intravenous vancomycin or daptomycin
Participants with known or suspected creatinine clearance (CLcr) < 30 milliliters per minute (mL/min)
In skilled nursing facility
In hospice or admission to hospice is planned
Intervention: Cholecalciferol
Trial phase: Not Applicable
ATC code: A11CC05 | A11CC55 | M05BB03 | M05BB04 | M05BB05 | M05BB07 | M05BB08 | M05BB09 | M05BX53
SMILES: [H][C@@]12CC[C@]([H])([C@H](C)CCCC(C)C)[C@@]1(C)CCC/C2=C\C=C1\C[C@@H](O)CCC1=C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 116
Group description: Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion).

Cholecalciferol: 50,000 IU PO weekly x 6 weeks
Eligibility criteria:
Inclusion Criteria:

Age > 18 years
Chronic hemodialysis treatments for at least 2 consecutive months
25OH-Vitamin D level < 25 ng/mL (inclusion criteria for randomization)

Exclusion Criteria:

History of acute renal failure requiring dialysis with potential for renal recovery
History of HIV/AIDS
Inability to provide informed consent
Intervention: Humalog
Trial phase: Phase 4
SMILES: CCC(C)C(NC(=O)CN)C(=O)NC(C(=O)NC(CCC(=O)O)C(=O)NC(CCC(N)=O)C(=O)NC1CSSCC2NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(CSSCC(NC(=O)C(CC(C)C)NC(=O)C(Cc3c[nH]cn3)NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)NC(CO)C(=O)NC(Cc3c[nH]cn3)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCC(=O)O)C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(Cc3ccc(O)cc3)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(C(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(Cc3ccccc3)C(=O)NC(Cc3ccccc3)C(=O)NC(Cc3ccc(O)cc3)C(=O)NC(C(=O)NC(CCCCN)C(=O)N3CCCC3C(=O)NC(C(=O)O)C(C)O)C(C)O)CSSCC(C(=O)NC(CC(N)=O)C(=O)O)NC(=O)C(Cc3ccc(O)cc3)NC(=O)C(CC(N)=O)NC(=O)C(CCC(=O)O)NC(=O)C(CC(C)C)NC(=O)C(CCC(N)=O)NC(=O)C(Cc3ccc(O)cc3)NC(=O)C(CC(C)C)NC(=O)C(CO)NC2=O)NC1=O)C(C)C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 197
Group description: Twice daily (before breakfast and lunch) insulin lispro mix 50 (LM50) and once daily (before dinner) insulin lispro mix 25 (LM25)

Insulin Lispro Mix: Participant dependent dose, administered subcutaneously for 24 weeks
Eligibility criteria:
Inclusion Criteria:

Present with type 2 diabetes mellitus
Have been receiving twice-daily premixed insulin therapy with or without metformin and/or alpha-glucosidase inhibitors, for at least six months prior to study entry
Have Haemoglobin A1c (HbA1c) >7.0% and <12.0%

Exclusion Criteria:

Within the last 3 months prior to entry into the study, are taking any non-permitted glucose-lowering agents, or are taking any non-permitted oral antihyperglycaemic medications
Are pregnant or intend to become pregnant during the course of the study, or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable.
Are women who are breastfeeding.
Have an irregular sleep/wake cycle (for example, participants who sleep during the day and work during the night).
Do not regularly consume three meals per day.
Have a body mass index >35 kilogram per square meter (kg/m^2).
Have had more than one episode of severe hypoglycaemia within 24 weeks prior to entry into the study.
Have cardiac disease with a functional status that is Class III or IV
Have a history of renal or liver disease
Have used less than or equal to 20 Units per day (U/day) of insulin during the past 90 days for more than 14 days (accumulated).
Intervention: Fluciclovine (18F)
Trial phase: Phase 2
ATC code: V09IX12
SMILES: N[C@]1(C(=O)O)C[C@@H]([18F])C1
Sex: Male
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 22
Group description: GE-148 (18F) : All subjects will receive an i.v. dose of GE-148 (18F) Injection at 10 mCi (370 MBq) to provide adequate image quality throughout the specified imaging period.

Efficacy analyses were not performed because GE Healthcare terminated the study early for administrative reasons.
Eligibility criteria:
INCLUSION CRITERIA:
Subject is male and is greater than or equal to 18 years old.
Subject must be scheduled to undergo standard of care prostatectomy for presumed localized prostate cancer at the NIH Clinical Center.
Recent (within 12 months of study entry but not within 8-12 weeks before start of imaging study) prostate biopsy indicating the presence of adenocarcinoma of the prostate gland in which at least sextant biopsies were obtained.
Subjects must have a minimum of 1 positive-for-cancer biopsy core.
Serum creatinine within 2 weeks prior to MR imaging less than or equal to 1.8 mg/dl and eGFR must be greater than 30 ml/min/1.73m(2)
Chemistry parameters: AST and ALT 2 x of the upper limits of normal; total bilirubin, of less than or equal to 2 x the upper limits of normal or less than 3.0 mg/dl in patients with Gilbert's syndrome.
Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2.
Ability to provide informed consent. All subjects must sign an informed consent form indicating their understanding of the investigational nature and risks of the study before any protocol-related studies are performed.
The subject has a clinically acceptable medical history, physical examination and vital signs findings during the screening period (from within 21 days before administration of GE-148 (18F) Injection).

EXCLUSION CRITERIA:

Known allergy to gadolinium.
Subjects for whom participating would significantly delay the scheduled standard of care therapy.
Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results.
Subjects with severe claustrophobia unresponsive to oral anxiolytics.

Subjects with contraindications to MRI

Subjects weighing more than 136 kg (weight limit for scanner table).
Subjects with pacemakers, cerebral aneurysm clips, shrapnel injury, or other implanted electronic devices or metal not compatible with MRI.

Subjects with contraindication to endorectal coil placement

Severe hemorrhoids.
Surgically absent rectum.
Other medical conditions deemed by the principle investigator (or associates) or sponsor to make the subject ineligible for protocol procedures.
Subjects who have previously received radiation therapy to the pelvis.
Subjects who have received androgen-deprivation therapy.
The subject has received, or is scheduled to receive, another IMP from 1 month before to 1 week after administration of GE-148 (18F) Injection.
Subjects with chronic renal failure (eGFR less than 30 ml/min/1.73m(2)).
Intervention: BENZOYL PEROXIDE
Trial phase: Not Applicable
ATC code: D10AE01 | D10AE51
SMILES: O=C(OOC(=O)c1ccccc1)c1ccccc1
Sex: All
Age groups: Child | Adult
Healthy volunteers: No
Participants at risk: 20
Group description: Subjects will receive standard-of-care treatment with the study medication, without internet surveys. Standard-of-care will mean patients are directed to take the medication daily and return for visits at 6 and 12 weeks.
Eligibility criteria:
Inclusion Criteria:

male or female 13 to 18 years of age with a diagnosis of mild to moderate acne vulgaris by a dermatologist.
written consent of participation must be given by parent or guardian and child.

Exclusion Criteria:

Age less than 13 or greater than 18 years of age.
Known allergy or sensitivity to topical benzoyl peroxide gel in the subject.
Inability to complete all study-related visits.
Introduction of any other prescription medication, topical or systemic, for acne vulgaris while participating in the study.
Subjects may not use topical retinoids or other benzoyl peroxide products, including Proactiv® or topical prescription medications while enrolled in the study.
Women that are actively trying to become pregnant or wish to become pregnant during the time frame the study is to take place will be excluded.
Subjects will be carefully selected for this study and only those deemed appropriate for treatment with benzoyl peroxide will be placed on this medication.
Intervention: Ganfort
Trial phase: Phase 3
SMILES: CC(C)(C)NCC(O)COc1nsnc1N1CCOCC1.CCNC(=O)CCCC=CCC1C(O)CC(O)C1C=CC(O)CCc1ccccc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 282
Group description: One drop of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (Ganfort®) administered in each eye every morning for 12 weeks.
Eligibility criteria:
Inclusion Criteria:

Patient has ocular hypertension or glaucoma in both eyes
Requires IOP-lowering therapy in each eye

Exclusion Criteria:

Active or recurrent eye disease that would interfere with interpretation of study data in either eye
History of any eye surgery or laser in either eye within 6 months
Required chronic use of other eye medications during the study
Anticipated wearing of contact lenses during the study.
Intermittent use of oral, intramuscular, or intravenous corticosteroids within 21 days
Intervention: Carvedilol
Trial phase: Phase 3
ATC code: C07AG02 | C07FX06
SMILES: COc1ccccc1OCCNCC(O)COc1cccc2[nH]c3ccccc3c12
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 121
Group description: up to 25 mg b.i.d.
Eligibility criteria:
Inclusion Criteria:

heart failure II-III
ischemic origin
stable medications from at least 3 months
> 3 months from an acute ischemic syndrome or revascularization procedure
naive on heart rate reducing agents

Exclusion Criteria:

bradycardia
hypersensitivity or contraindications to study drugs
exercise tolerance at 6 minute walking test <100 m or >400 m
Intervention: Azithromycin
Trial phase: Not Applicable
ATC code: J01FA10 | J01RA07 | J01RA16 | S01AA26
SMILES: CCC1OC(=O)C(C)C(OC2CC(C)(OC)C(O)C(C)O2)C(C)C(OC2OC(C)CC(N(C)C)C2O)C(C)(O)CC(C)CN(C)C(C)C(O)C1(C)O
Sex: All
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 42
Group description: DFA positive chlamydial conjunctivitis patients were orally administered azithromycin (400mg~1000mg, according to their age and body weight) once a week for consecutive two weeks, and the DFA tests were repeated 4 weeks after the treatment. If the DFA tests still showed positive results, an additional dose of azithromycin was orally administered, and another DFA test was performed again 4 weeks later. The augmented treatment with oral azithromycin (administration of one oral dose followed by DFA testing 4 weeks later) was continued until the DFA tests showed negative results.
Eligibility criteria:
Inclusion Criteria:

Patients of clinically chlamydial conjunctivitis suspected and proven by direct fluorescent antibody(DFA)results

Exclusion Criteria:

Patients with pregnancy or lactation, history of allergy to macrolides, evidence or history of hepatic, renal, hematological or cardiovascular disease
Intervention: Victoza
Trial phase: Phase 3
ATC code: A10BJ02
SMILES: CCCCCCCCCCCCCCCC(=O)NC(CCC(=O)NCCCCC(NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(=O)O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)C(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(CCC(=O)O)C(=O)NC(Cc1ccccc1)C(=O)NC(C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)O)C(C)C)C(C)CC)C(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 4668
Group description: Subjects received liraglutide once daily by subcutaneous injection in the abdomen, thigh or upper arm, at any time of the day and irrespective of meals, for a treatment period of 42 to 60 months. It was recommended to keep the time of injection consistent from day to day. Liraglutide was initiated at a dose of 0.6 mg and up-titrated to 1.2 mg after 1 week and to 1.8 mg after one additional week up to 42-60 months.
Eligibility criteria:
Inclusion Criteria: - Type 2 diabetes - Age min. 50 years at screening and concomitant cardiovascular, cerebrovascular or peripheral vascular disease or chronic renal failure or chronic heart failure OR age min. 60 years at screening and other specified risk factors of cardiovascular disease - HbA1c: 7.0% or above - Anti-diabetic drug naive or treated with one or more oral anti-diabetic drugs (OADs) or treated with human NPH insulin or long-acting insulin analogue or premixed insulin, alone or in combination with OAD(s) Exclusion Criteria: - Type 1 diabetes - Use of a glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide or other) or pramlintide or any dipeptidyl peptidase 4 (DPP-4) inhibitor within the 3 months prior to screening (trial start) - Use of insulin other than human NPH insulin or long-acting insulin analogue or premixed insulin within 3 months prior to screening. Short-term use of other insulin during this period in connection with intercurrent illness is allowed, at Investigator's discretion