anthonyyazdaniml/CT-ADE-SOC huggingface dataset:
Intervention: Donepezil
Trial phase: Phase 4
ATC code: N06DA02 | N06DA52 | N06DA53
SMILES: COc1cc2c(cc1OC)C(=O)C(CC1CCN(Cc3ccccc3)CC1)C2
Sex: All
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 18
Group description: Donepezil: Use 1 capsule (5 mg) of donepezil once per day for first 21 days than donepezil 10mg qday for 21 days in either the first or last 6 weeks of the study.
Eligibility criteria:
Inclusion Criteria:

Idiopathic Parkinson's disease, defined by the UK Brain Bank criteria, with a Hoehn and Yahr score of 2 to 4
Treated with levodopa for at least a year and on a stable antiparkinsonian regimen for at least one month
Abnormal computerized dynamic posturography (CDP) on screening defined as a composite score below 65 (range 1-100)

Exclusion Criteria:

Dementia defined by MMSE less than 27
Other medical conditions other than PD affecting balance or gait as determined by the investigators
Unable to stand unassisted for 30 minutes
Current use of an acetylcholinesterase inhibitors or drugs with known anticholinergic properties
Medical or psychiatric co-morbidities that may interfere with compliance or might place subject in danger as determined by the investigators
Intervention: 6-Acryloyloxyhexyl phosphate
Trial phase: Phase 2
SMILES: C=CC(=O)OCCCCCCO.O=P(O)(O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 39
Group description: PA21
Eligibility criteria:
Inclusion Criteria:

Patients age 20 or older, regardless of gender.
Receiving stable maintenance hemodialysis 3 times a week.
Patients not having changed their phosphate binder agent dose, for 4 weeks or more before their observation period start.

Exclusion Criteria:

Patients having history of a pronounced brain / cardiovascular disorder.
Patients having severe gastrointestinal disorders.
Patients having severe hepatic disorders.
Intervention: 6-Acryloyloxyhexyl phosphate
Trial phase: Phase 2
SMILES: C=CC(=O)OCCCCCCO.O=P(O)(O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 36
Group description: PA21
Eligibility criteria:
Inclusion Criteria:

Patients age 20 or older, regardless of gender.
Receiving stable maintenance hemodialysis 3 times a week.
Patients not having changed their phosphate binder agent dose, for 4 weeks or more before their observation period start.

Exclusion Criteria:

Patients having history of a pronounced brain / cardiovascular disorder.
Patients having severe gastrointestinal disorders.
Patients having severe hepatic disorders.
Intervention: 6-Acryloyloxyhexyl phosphate
Trial phase: Phase 2
SMILES: C=CC(=O)OCCCCCCO.O=P(O)(O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 35
Group description: PA21
Eligibility criteria:
Inclusion Criteria:

Patients age 20 or older, regardless of gender.
Receiving stable maintenance hemodialysis 3 times a week.
Patients not having changed their phosphate binder agent dose, for 4 weeks or more before their observation period start.

Exclusion Criteria:

Patients having history of a pronounced brain / cardiovascular disorder.
Patients having severe gastrointestinal disorders.
Patients having severe hepatic disorders.
Intervention: Eplerenone
Trial phase: Not Applicable
ATC code: C03DA04
SMILES: [H][C@@]12CC[C@@]3(CCC(=O)O3)[C@@]1(C)C[C@H]1O[C@@]13[C@@]2([H])[C@H](C(=O)OC)CC1=CC(=O)CC[C@@]13C
Sex: Male
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 20
Group description: eplerenone one tablet daily for 12 months
Eligibility criteria:
Inclusion Criteria:

DMD patients age 7 years and older (and able to complete cardiac MRI without sedation) with preserved left ventricular (LV) systolic function and abnormal heart muscle by late post-gadolinium imaging (LGE)

Exclusion Criteria:

renal insufficiency (GFR <40 mL/min/m2)
non-MR compatible implants (e.g. neurostimulator, AICD)
severe claustrophobia
allergy to gadolinium contrast
prior use of or known allergy to epleronone
use of potassium-sparing diuretics
serum potassium level of >5.0 mmol/L
Intervention: Capsaicin
Trial phase: Phase 3
ATC code: M02AB01 | M02AB02 | N01BX04
SMILES: COc1cc(CNC(=O)CCCC/C=C/C(C)C)ccc1O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 104
Group description: receive omega 3 in addition to standard treatment
Eligibility criteria:
Inclusion Criteria:

candidate of elective PCI
treatment with aspirin at least 5 days before PCI

Exclusion Criteria:

high CKMB and troponin I level
cardiac bypass in recent 3 months
platelet count < 70×10 9/L
sever chronic renal failure
active bleeding
treatment with glycoprotein IIb/IIIa inhibitors during PCI
treatment with bivalirudin during PCI
sensitivity to aspirin and clopidogrel
Intervention: Epiduo
Trial phase: Phase 4
SMILES: COc1ccc(-c2ccc3cc(C(=O)O)ccc3c2)cc1C12CC3CC(CC(C3)C1)C2.O=C(OOC(=O)c1ccccc1)c1ccccc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 73
Group description: Fixed dose of adapalene 0.1% and benzoyl peroxide 2.5% gel

Epiduo Gel : Fixed dose of adapalene 0.1% and benzoyl peroxide 2.5% in an aqueous based gel.
Eligibility criteria:
Inclusion Criteria:

Male and female subjects of any race
Subjects 18 years or older
Subjects with acne vulgaris

Exclusion Criteria:

Subjects with an allergy to a component of the study drugs (refer to the package inserts for Epiduo Gel and Retin-A Micro 0.1%)
Subjects with a washout period for topical treatment (less than 1 week for corticosteroids or 4 weeks for retinoids)
Subjects with a washout period for systemic treatment (less than 1 week for medications that may have increased photosensitivity or 4 weeks for corticosteroids or 24 weeks for oral retinoids)
Subjects with a sunburn, eczema, atopic dermatitis, perioral dermatitis, rosacea, or other topical conditions on the treatment area
Subjects with planned unprotected and intense UV exposure during the study (mountain sports, UV radiation, sunbathing, etc)
Intervention: Nebivolol
Trial phase: Phase 2
ATC code: C07AB12 | C07BB12 | C07FB12 | C09DX05
SMILES: OC(CNCC(O)C1CCc2cc(F)ccc2O1)C1CCc2cc(F)ccc2O1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 20
Group description: 5 mg, continue for 1 month; dose titration to 10 mg, continue for 8 months. Dose may be returned to initiation levels if side effects occur.

Nebivolol: 5 mg daily or 10 mg daily
Eligibility criteria:
Inclusion Criteria:

borderline blood pressure (120-145/80-90 mm Hg);
borderline or abnormal small artery elasticity (C2) as measured by pulse contour analysis;
treatment-naive for all blood pressure medications including diuretics for at least 30 days prior to baseline visit;
able to walk on a treadmill for 3 minutes;
female patients with reproductive potential must use an approved contraceptive method if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device during and for 1 month after the last dose of study drug;
voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

history of intolerance to beta-blockers or clear contraindications to their use; current pharmaceutical treatment of blood pressure;
known history of cardiovascular disease (myocardial infarction, coronary artery bypass graft, unstable angina, uncontrolled arrhythmias, stroke, etc.);
known history of diabetes; known history of hepatic, renal or gastrointestinal disorder;
known history of any illness that may cause additional risk (as determined by study investigator);
pregnant or lactating women [when used during pregnancy, beta-blockers may cause fetal harm];
participation in a concomitant clinical trial.
Intervention: Atenolol
Trial phase: Phase 2
ATC code: C07AB03 | C07BB03 | C07CB03 | C07CB53 | C07DB01 | C07FB03
SMILES: CC(C)NCC(O)COc1ccc(CC(N)=O)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 18
Group description: 25 mg, continue for 1 month; dose titration to 50 mg, continue for 8 months. Dose may be returned to initiation levels if side effects occur.

atenolol: 25 mg daily or 50 mg daily
Eligibility criteria:
Inclusion Criteria:

borderline blood pressure (120-145/80-90 mm Hg);
borderline or abnormal small artery elasticity (C2) as measured by pulse contour analysis;
treatment-naive for all blood pressure medications including diuretics for at least 30 days prior to baseline visit;
able to walk on a treadmill for 3 minutes;
female patients with reproductive potential must use an approved contraceptive method if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device during and for 1 month after the last dose of study drug;
voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

history of intolerance to beta-blockers or clear contraindications to their use; current pharmaceutical treatment of blood pressure;
known history of cardiovascular disease (myocardial infarction, coronary artery bypass graft, unstable angina, uncontrolled arrhythmias, stroke, etc.);
known history of diabetes; known history of hepatic, renal or gastrointestinal disorder;
known history of any illness that may cause additional risk (as determined by study investigator);
pregnant or lactating women [when used during pregnancy, beta-blockers may cause fetal harm];
participation in a concomitant clinical trial.
Intervention: Ticagrelor
Trial phase: Phase 4
ATC code: B01AC24
SMILES: CCCSc1nc(N[C@@H]2C[C@H]2c2ccc(F)c(F)c2)c2nnn([C@@H]3C[C@H](OCCO)[C@@H](O)[C@H]3O)c2n1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 34
Group description: Ticagrelor 180 mg loading dose followed by 90 mg bd for 7, 8 or 9 days
Eligibility criteria:
Inclusion Criteria:

Provision of signed and dated informed consent before initiation of any study-related procedures
Male or female patients aged 18 years or older
Documented stable CAD fulfilling and taking 75-100mg ASA daily treatment
Females must be post menopausal or surgically sterile Self-identified as African American

Exclusion Criteria:

Any indication for oral anticoagulant (e.g., atrial fibrillation, mitral stenosis or prosthetic heart valve) or dual antiplatelet treatment (e.g., clopidogrel, prasugrel, ASA dose other than 75 to 100 mg daily) during study period
Patients who had ACS or stent placed within 12 months of screening Patients with a history of moderate or severe hepatic impairment
Current smokers, including the use of tobacco containing products in the past 1 month of randomization Patients required dialysis
Intervention: Clopidogrel
Trial phase: Phase 4
ATC code: B01AC04
SMILES: [H][C@@](C(=O)OC)(c1ccccc1Cl)N1CCc2sccc2C1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 31
Group description: Clopidogrel 600 mg loading dose followed by 75 mg od for 7, 8 or 9 days
Eligibility criteria:
Inclusion Criteria:

Provision of signed and dated informed consent before initiation of any study-related procedures
Male or female patients aged 18 years or older
Documented stable CAD fulfilling and taking 75-100mg ASA daily treatment
Females must be post menopausal or surgically sterile Self-identified as African American

Exclusion Criteria:

Any indication for oral anticoagulant (e.g., atrial fibrillation, mitral stenosis or prosthetic heart valve) or dual antiplatelet treatment (e.g., clopidogrel, prasugrel, ASA dose other than 75 to 100 mg daily) during study period
Patients who had ACS or stent placed within 12 months of screening Patients with a history of moderate or severe hepatic impairment
Current smokers, including the use of tobacco containing products in the past 1 month of randomization Patients required dialysis
Intervention: Sertraline
Trial phase: Phase 4
ATC code: N06AB06
SMILES: CN[C@H]1CC[C@@H](c2ccc(Cl)c(Cl)c2)c2ccccc21
Sex: All
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 71
Group description: 24 weeks of sertraline + enhanced medication management

Sertraline: Initial baseline dose of 25 mg/day. Clinician will attempt to titrate patients to at least 100 mg/day and up to 200 mg/day if tolerated by week 8.
Eligibility criteria:
Inclusion Criteria:

Patient is an Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) combat veteran with chronic posttraumatic stress disorder (PTSD) or significant PTSD symptoms (Clinician Administered Posttraumatic Stress Disorder Scale [CAPS] >= 50) of at least 3 months duration

Exclusion Criteria:

Current, imminent risk of suicide (as indicated on C-SSRS)
Active psychosis
Alcohol or substance dependence in the past 8 weeks
Unable to attend regular appointments
Prior intolerance or failure of adequate trial of prolonged exposure (PE) or sertraline (SERT) (defined as at least 2 months of SERT at least 100mg/day)
Medical illness likely to result in hospitalization or for which treatments are contraindicated (based on lab results, medical history and physical exam)
Serious cognitive impairment (as evidenced by cognitive impairment felt likely to interfere with the ability to participate meaningfully in the study)
Concurrent antidepressants or antipsychotics
Pregnant females
Intervention: Budesonide
Trial phase: Phase 2 | Phase 3
ATC code: A07EA06 | D07AC09 | R01AD05 | R03AK07 | R03AK12 | R03AL11 | R03BA02
SMILES: CCCC1OC2CC3C4CCC5=CC(=O)C=CC5(C)C4C(O)CC3(C)C2(C(=O)CO)O1
Sex: All
Age groups: Child
Healthy volunteers: No
Participants at risk: 458
Group description: Subjects with acute asthma exacerbation who receive Budesonide 500 mcg, in addition to Albuterol 2.5 mg if < 20 kg body weight or 5 mg if >= 20 kg body weight and Ipratropium Bromine (IB) 250 mcg; 3 nebulization doses back to back
Eligibility criteria:
Inclusion Criteria:

Children 2-12 years of age with physician diagnosed asthma or a previous episode of SOB that responded well to β2-agonists who present to the ER with moderate or severe asthma exacerbation

Exclusion Criteria:

Children with mild asthma exacerbation.
Children with severe asthma exacerbation who are in critical condition or need immediate intervention.
Children who have heart disease or chronic lung disease other than asthma.
Systemic steroids administered within the past 7 days.
Intervention: Ofloxacin
Trial phase: Phase 4
ATC code: A02BD10 | J01MA01 | J01MA12 | J01RA05 | J01RA09 | S01AE01 | S01AE05 | S02AA16
SMILES: CC1COc2c(N3CCN(C)CC3)c(F)cc3c(=O)c(C(=O)O)cn1c23
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 12
Group description: Pharmacodynamics

Levofloxacin: 750 mg QD
Eligibility criteria:
Inclusion Criteria:

non-pregnant adults (≥ 18 years old) with suspected CABP admitted to the hospital for parenteral antibiotic therapy.
All patients will have a creatinine clearance (CrCl) >50 ml/min.

Exclusion Criteria:

pregnant or nursing patients,
allergy to penicillin/cephalosporin antibiotics,
allergy to fluoroquinolones,
renal or hepatic failure, or have received an antimicrobial in past 96h.
Patients who require antibiotics other than the study drugs will also be excluded.
Intervention: CEFTAROLINE FOSAMIL
Trial phase: Phase 4
ATC code: J01DI02
SMILES: [H][C@]12SCC(Sc3nc(-c4cc[n+](C)cc4)cs3)=C(C(=O)[O-])N1C(=O)[C@H]2NC(=O)/C(=N\OCC)c1nsc(NP(=O)(O)O)n1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 12
Group description: Pharmacodynamics

Ceftaroline: 600 mg Q12h
Eligibility criteria:
Inclusion Criteria:

non-pregnant adults (≥ 18 years old) with suspected CABP admitted to the hospital for parenteral antibiotic therapy.
All patients will have a creatinine clearance (CrCl) >50 ml/min.

Exclusion Criteria:

pregnant or nursing patients,
allergy to penicillin/cephalosporin antibiotics,
allergy to fluoroquinolones,
renal or hepatic failure, or have received an antimicrobial in past 96h.
Patients who require antibiotics other than the study drugs will also be excluded.
Intervention: Prednisone
Trial phase: Phase 4
ATC code: A07EA03 | H02AB07
SMILES: [H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)CC(=O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@@]21C
Sex: All
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 23
Group description: A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) was administered to all participants. The following day, participant began glucocorticoid therapy of prednisone 30 mg oral daily for one week followed by a standardized taper until a minimally effective dose was achieved or participant tapered to prednisone 5 mg oral daily.
Eligibility criteria:
SUBJECT INCLUSION CRITERIA:

Subjects on Protocol #94-I-0079 will be eligible for participation in the study only if all of the following criteria apply:

Subjects must be 7 years of age or older to enroll
Subject meets diagnostic criteria for HES (AEC >1500/microL, absence of a secondary cause and signs and/or symptoms attributable to the eosinophilia)
AEC greater than 1500 microL obtained within 14 days prior to enrollment
Willingness to perform the timed steroid challenge
Appropriate candidate for GC treatment after challenge
Willingness to have samples stored for future research

SUBJECT EXCLUSION CRITERIA:

A subject will not be eligible to participate in the study if any of the following apply:

Receiving >10 mg prednisone or equivalent at the time of enrollment.
Receiving less than or equal to 10 mg of prednisone or equivalent but have not been on a fixed dose for at least 3 weeks (subjects on a current corticosteroid taper will be excluded).
AEC less than or equal to 1500/microl on the day of the steroid challenge
Use of immunomodulatory medications, (other than less than or equal to 10 mg/day prednisone) including but not limited to biologics, within the past 6 months.
Pregnant at the time of screening.
Have a known mutation in the FIP1L1-PDGFR gene.
Any condition that, in the opinion of the investigator, places the subject at undue risk by participating in the protocol.
Weight less than 48 kg (106 lbs) in subjects less than 18 years of age.
Intervention: Varenicline
Trial phase: Phase 2
ATC code: N07BA03 | S01XA28
SMILES: c1cnc2cc3c(cc2n1)C1CNCC3C1
Sex: All
Age groups: Adult
Healthy volunteers: No
Participants at risk: 21
Group description: Subjects will receive either varenicline or placebo

Varenicline or placebo: Varenicline or placebo will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks.
Eligibility criteria:
Inclusion Criteria:

Physically healthy male or female nicotine dependent patients ages 18-60 without other current drug dependence or psychiatric diagnosis.
Smoke ≥ 10 cigarettes per day for at least 6 months prior to study start date.
Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 1 year post-menopausal) or of child bearing potential but practicing a medically acceptable method of birth control from at least 2 weeks prior to screening until 30 days after the last dose of varenicline. Examples of medically acceptable methods for this protocol include barrier (diaphragm or condom) with spermicide, an intrauterine (IUD), oral contraceptives, levonorgestrel implant, or complete abstinence.
Subjects provide voluntary informed consent.
Subjects must read at 8th grade level or higher.

Exclusion Criteria:

History of head trauma or injury causing loss of consciousness, lasting more than three (3) minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI.
Presence of magnetically active prosthetics, plates, pins, permanent retainer, bullets, etc. in patient's body (unless a radiologist confirms that it's presence is unproblematic). An x-ray may be obtained to determine eligibility given the possibility of a foreign body.
Self report of HIV positive and on medication for symptoms: Determined on an individual basis by results from the physical examination and final approval by the study physician.
Symptomatic presence of other hematological disease.
Clinically significant hepatic (liver), renal (kidney), neurological, or endocrinological abnormalities.
History of any cardiovascular event within the last 6 months and any serious/significant cardiovascular event in the subject's life. This will be determined on an individual basis by the study physician.
History of psychosis or seizures.
Use of medications or natural herbs that may cause sedation or may effect the brain systems that are being studied (medication use will be evaluated on a case-by-case basis).
Claustrophobia or other medical condition preventing subject from lying in the MRI for approximately one (1) hour.
Intervention: Betamethasone Sodium Phosphate
Trial phase: Phase 4
SMILES: CC1CC2C3CCC4=CC(=O)C=CC4(C)C3(F)C(O)CC2(C)C1(O)C(=O)COP(=O)([O-])[O-].[Na+].[Na+]
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 102
Group description: Participants in this group received 1mL of Celestone (6mg/mL) injected into the the superior joint space.
Eligibility criteria:
Inclusion Criteria:

age greater than 18 years
arthralgia of one or both temporomandibular joints
Wilkes II to IV internal derangement of the symptomatic joint OR
limited opening of <35 mm

Exclusion Criteria:

myofascial pain as the primary source of pain

cervical pain as the primary source of pain
systemic arthropathy
fibromyalgia
use of NSAIDS within 48 hours
allergy to study medications
edentulous subjects
pregnancy or breast feeding
current physical therapy, muscle relaxants or antiseizure medications
current use of a splint issued within last 12 weeks
Intervention: Hyaluronic acid
Trial phase: Phase 4
ATC code: D03AX05 | M09AX01 | R01AX09 | S01KA01 | S01KA51
SMILES: CC(=O)N[C@@H]1C(O[C@@H]2O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](OC2[C@@H](NC(C)=O)[C@H](O)O[C@H](CO)[C@H]2O)O[C@@H]1C(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 102
Group description: Participants in the group received 1mL of Hyalgan (10 mg/mL) injected into the superior joint space.
Eligibility criteria:
Inclusion Criteria:

age greater than 18 years
arthralgia of one or both temporomandibular joints
Wilkes II to IV internal derangement of the symptomatic joint OR
limited opening of <35 mm

Exclusion Criteria:

myofascial pain as the primary source of pain

cervical pain as the primary source of pain
systemic arthropathy
fibromyalgia
use of NSAIDS within 48 hours
allergy to study medications
edentulous subjects
pregnancy or breast feeding
current physical therapy, muscle relaxants or antiseizure medications
current use of a splint issued within last 12 weeks
Intervention: Dapagliflozin
Trial phase: Phase 1
ATC code: A10BD15 | A10BD21 | A10BD25 | A10BK01
SMILES: CCOc1ccc(Cc2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)ccc2Cl)cc1
Sex: All
Age groups: Child
Healthy volunteers: No
Participants at risk: 8
Group description: Dapagliflozin: Tablet, Oral, 5 mg, Single-dose
Eligibility criteria:
Inclusion Criteria:

Clinical diagnosis of T2DM
Male and female subjects ages 10-17
Glycosylated Hemoglobin A1c (HbA1c) ≥6 to 10%
Body weight ≥30 kg

Exclusion Criteria:

Fasting plasma glucose (FPG) >240 mg/dL at screening
Abnormal renal function
Active liver disease and/or significant abnormal liver function