Study of Pharmacodynamics and Safety of DGAT2i and ACCi Coadministered in Participants With Sponsor-defined Presumed Non Alcoholic Steatohepatitis

Percent CFB in Fasting Serum Triglycerides at Week 6

Blood samples were collected before morning dose for the measurement of fasting serum triglycerides. Natural log transformed relative changes from baseline in fasting serum triglycerides were analyzed using mixed model repeated measures (MMRM) analysis with treatment, week and treatment by-week interaction as fixed effects, participant as random effect and log transformed baseline as a covariate using unstructured covariance structure. Values were back-transformed from the log scale. Relative change was converted to percent change as follows: Percent change = 100\*(RC-1). For this OM, baseline is defined as the result closest prior to dosing on Day 1 (either predose on Day 1/Visit 4 or Week -2/Visit 3).

Time frame: Baseline, Week 6

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=all AEs included in the AE Case Report Form (CRF) page during the study. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; or resulted in congenital anomaly/birth defect. Severe TEAEs were defined as AEs that prevent normal everyday activities. Treatment-related TEAEs were determined by the investigator.

Time frame: Baseline up to at least 28 days after the last administration of the study intervention or until study completion or withdrawal, whichever was longer (maximum of approximately 24 weeks).

Number of Participants With TEAEs of Special Interest by Preferred Term (PT)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=all AEs included in the AE CRF page during the study. A 3-tier approach was used to summarize and classify TEAEs into 1 of 3 tiers by the investigator based on their incidence rate and clinical importance to the trial. Tier-1 events = pre-specified events of clinical importance that are maintained in a program level list. Tier-2 events = events that are not tier-1 but are "common". A Medical Dictionary for Regulatory Activities Terminology (MedDRA) PT is defined as a tier-2 event if there are at least 4 participants with at least one occurrence in any treatment group, to distinguish Tier-2 events from Tier-3 events. Tier-3 events = events that do not meet criteria for either tier-1 or tier-2 event. TEAE(s) of special interest reported in at least 1 participant are presented in this OM.

Time frame: Baseline up to at least 28 days after the last administration of the study intervention or until study completion or withdrawal, whichever was longer (maximum of approximately 24 weeks).

Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality

Participants with laboratory test abnormalities (hematology, chemistry and urinalysis) meeting pre-specified criteria are reported without regard to baseline abnormality. LLN is lower limit of normal. ULN is upper limit of normal. Baseline was defined as the result closest prior to Day 1 dosing.

Time frame: From baseline to end of follow-up or until study discontinuation/withdrawal, whichever was longer (maximum of approximately 19 weeks)

Number of Participants With Abnormalities in Laboratory Parameters of Special Interest Meeting Pre-Defined Criteria

Laboratory parameters of special interest included fasting serum triglycerides, platelet count, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, and fasting plasma glucose. Pre-specified criteria for laboratory parameters of special interest included flag level threshold (reflecting either the threshold for study entry or clinical significance) and alert level threshold (requiring rapid notification to site and study team when values exceeding the threshold were noted during the study). All flag level changes and alert level changes were cumulative from baseline (defined as result closest prior to dosing at Day 1). LLN is lower limit of normal. ULN is upper limit of normal.

Time frame: From baseline to end of follow-up or until study discontinuation/withdrawal, whichever was longer (maximum of approximately 19 weeks)

Number of Participants With Post-Baseline Vital Signs Data Meeting Pre-Defined Criteria

Pre-defined categorical criteria for vital signs data of special clinical concern included: seated systolic blood pressure (BP) absolute value \<90 mmHg or change from baseline \>=30 mmHg, seated diastolic BP absolute value \<50 mmHg or change from baseline \>=20 mmHg, seated pulse rate absolute value \<40 beats per minute (bpm) or \>120 bpm. Baseline was defined as the result closest prior to Day 1 dosing.

Time frame: Baseline, Week 6, the first follow-up visit (Week 8), and the date of discontinuation/withdrawal from study (maximum of approximately 12 weeks after Day 1) if applicable

Number of Participants With Post-Baseline Electrocardiogram (ECG) Data Meeting Pre-Defined Criteria

Pre-defined categorical criteria for ECG data of special clinical concern included: (1) QTc interval absolute value \>450 and \<=480 msec (mild prolongation), \>480 and \<=500 msec (moderate prolongation), \>500 msec (severe prolongation); (2) QTc interval increase from baseline \>=30 and \<=60 msec (moderate prolongation), or \>60 msec (severe prolongation); (3) uncorrected QT interval \>500 msec. ECG abnormalities meeting prespecified criteria and reported in at least 1 participant are presented in this OM. Baseline was defined as the result closest prior to Day 1 dosing.

Time frame: Baseline, Week 6, the first follow-up visit (Week 8), and the date of discontinuation/withdrawal from study (maximum of approximately 12 weeks after Day 1) if applicable