Phase 1
Completed N=16
Study to Evaluate the Pharmacokinetic (PK) Interactions Between GSK3640254 and Dolutegravir (DTG)
Source: ClinicalTrials.gov NCT03816696 ↗Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Mar 2020
Primary outcomePrimary: Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing (AUC[0 to Tau]) of Dolutegravir for Dolutegravir Arm — 64627.8 Hours* nanogram per milliliter
Summary
This is an open-label, single-sequence, two-way drug interaction study to investigate the PK, safety and tolerability of GSK3640254 and DTG when administered alone or in combination in healthy subjects. Treatment of human immunodeficiency virus (HIV) infection frequently involves combination therapy. Data from this study will contribute to dosing recommendations when GSK3640254 and DTG are given in combination. The study will consist of a Screening period and 3 sequential treatment periods. Subjects will be administered DTG 50 milligrams (mg) once daily (QD) in Period 1 followed by GSK3640254 200 mg QD in Period 2. There will be a washout period of 4 days between Periods 1 and 2. In Period 3, subjects will be co-administered DTG 50 mg QD and GSK3640254 200 mg QD. The total duration of the study will be approximately 55 days, including Screening.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing (AUC[0 to Tau]) of Dolutegravir for Dolutegravir Arm |
64627.8 | — |
| PRIMARY Period 3: AUC(0 to Tau) of Dolutegravir for Dolutegravir + GSK3640254 Arm |
75860.5 | — |
| PRIMARY Period 1: Maximum Observed Concentration (Cmax) of Dolutegravir for Dolutegravir Arm |
4962 | — |
| PRIMARY Period 3: Cmax of Dolutegravir for Dolutegravir + GSK3640254 Arm |
5408 | — |
| PRIMARY Period 1: Plasma Concentration at the End of the Dosing Interval (Ctau) of Dolutegravir for Dolutegravir Arm |
1373 | — |
| PRIMARY Period 3: Ctau of Dolutegravir for Dolutegravir + GSK3640254 Arm |
1696 | — |
| PRIMARY Period 2: AUC(0 to Tau) of GSK3640254 for GSK3640254 Arm |
26.72 | — |
| PRIMARY Period 3: AUC(0 to Tau) of GSK3640254 for Dolutegravir + GSK3640254 Arm |
27.84 | — |
| PRIMARY Period 2: Cmax of GSK3640254 for GSK3640254 Arm |
1.676 | — |
| PRIMARY Period 3: Cmax of GSK3640254 for Dolutegravir + GSK3640254 Arm |
1.662 | — |
| PRIMARY Period 2: Ctau of GSK3640254 for GSK3640254 Arm |
0.8583 | — |
| PRIMARY Period 3: Ctau of GSK3640254 for Dolutegravir + GSK3640254 Arm |
0.8549 | — |
| SECONDARY Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) |
1; 3; 2; 0; 0; 0 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count |
-0.003; 0.046; 0.013; -0.020; -0.217; -6.5 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count |
-0.006; -0.026; -0.154; -0.024; -0.160; -6.0 | — |
| SECONDARY Period 3: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count |
0.003; 0.007; 0.003; -0.001; 0.004; -0.036 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameter: Hemoglobin |
4.4 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameter: Hemoglobin |
0.1 | — |
| SECONDARY Period 3: Change From Baseline in Hematology Parameter: Hemoglobin |
3.3; 0.6; 1.2 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameter: Hematocrit |
0.0178 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameter: Hematocrit |
-0.0013 | — |
| SECONDARY Period 3: Change From Baseline in Hematology Parameter: Hematocrit |
0.0035; -0.0049; -0.0041 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameter: Erythrocytes |
0.170 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameter: Erythrocytes |
0.036 | — |
| SECONDARY Period 3: Change From Baseline in Hematology Parameter: Erythrocytes |
0.016; -0.079; -0.054 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume |
0.63 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume |
-0.86 | — |
| SECONDARY Period 3: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume |
0.40; 0.36; 0.05 | — |
| SECONDARY Period 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin |
-0.11 | — |
| SECONDARY Period 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin |
-0.17 | — |
| SECONDARY Period 3: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin |
0.55; 0.55; 0.52 | — |
| SECONDARY Period 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen |
0.063; 0.088; -0.084; -1.2; 0.025; -0.1 | — |
| SECONDARY Period 2: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen |
-0.249; -0.269; 0.087; 2.2; 0.014; -1.3 | — |
| SECONDARY Period 3: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen |
0.062; 0.103; -0.066; 0.096; -0.008; -0.030 | — |
| SECONDARY Period 1: Change From Baseline in Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase |
-32.0; -21.9; -0.3; -0.1; -0.7; -2.1 | — |
| SECONDARY Period 2: Change From Baseline in Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase |
22.6; 9.1; -0.6; 1.9; 0.2; -0.8 | — |
| SECONDARY Period 3: Change From Baseline in Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase |
-32.1; -37.1; -42.1; 5.9; -0.9; 0.1 | — |
| SECONDARY Period 1: Change From Baseline in Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin |
-32.3; 5.41; 0.01; 0.03 | — |
| SECONDARY Period 2: Change From Baseline in Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin |
-7.1; -3.36; 0.27; 0.06 | — |
| SECONDARY Period 3: Change From Baseline in Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin |
0.0; -15.6; -1.4; 7.90; 9.89; 1.99 | — |
| SECONDARY Period 1: Change From Baseline in Chemistry Parameters: Albumin, Globulin, Protein |
0.4; 0.8; 1.2 | — |
| SECONDARY Period 2: Change From Baseline in Chemistry Parameters: Albumin, Globulin, Protein |
0.9; -1.1; -0.2 | — |
| SECONDARY Period 3: Change From Baseline in Chemistry Parameters: Albumin, Globulin, Protein |
0.9; 0.2; 0.4; -0.9; 1.0; 0.5 | — |
| SECONDARY Period 1: Change From Baseline in Chemistry Parameters: Amylase, Lipase |
3.1; -3.4 | — |
| SECONDARY Period 2: Change From Baseline in Chemistry Parameters: Amylase, Lipase |
-2.8; -0.7 | — |
| SECONDARY Period 3: Change From Baseline in Chemistry Parameters: Amylase, Lipase |
-1.6; 0.1; -0.9; 4.7; -0.8; 0.1 | — |
| SECONDARY Period 1: Change From Baseline in Urinalysis Parameter: Specific Gravity |
0.0053 | — |
| SECONDARY Period 2: Change From Baseline in Urinalysis Parameter: Specific Gravity |
-0.0004 | — |
| SECONDARY Period 3: Change From Baseline in Urinalysis Parameter: Specific Gravity |
0.0003; -0.0007; -0.0016 | — |
| SECONDARY Period 1: Change From Baseline in Urinalysis Parameter: Urobilinogen |
0.0000 | — |
| SECONDARY Period 2: Change From Baseline in Urinalysis Parameter: Urobilinogen |
0.0000 | — |
| SECONDARY Period 3: Change From Baseline in Urinalysis Parameter: Urobilinogen |
0.0000; 0.0000; 0.0000 | — |
| SECONDARY Period 1: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) |
-0.22 | — |
| SECONDARY Period 2: Change From Baseline in Urinalysis Parameter: pH |
0.13 | — |
| SECONDARY Period 3: Change From Baseline in Urinalysis Parameter: pH |
0.03; -0.13; 0.16 | — |
| SECONDARY Period 1: Number of Participants With Urinalysis Dipstick Results |
16; 16; 15; 1; 16; 16 | — |
| SECONDARY Period 2: Number of Participants With Urinalysis Dipstick Results |
16; 16; 15; 1; 15; 1 | — |
| SECONDARY Period 3: Number of Participants With Urinalysis Dipstick Results |
16; 16; 16; 16; 16; 16 | — |
| SECONDARY Period 1: Change From Baseline in PR Interval, QRS Duration, QT Interval, Fridericia QT Correction Formula (QTcF), Bazett's QT Correction Formula (QTcB) |
-0.5; 1.7; 4.7; 1.3; 1.9; 1.8 | — |
| SECONDARY Period 2: Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcF, QTcB |
-3.3; -3.0; -2.1; -3.4; -6.4; 0.1 | — |
| SECONDARY Period 3: Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcF, QTcB |
1.9; -1.9; -0.4; 0.9; -2.9; -1.4 | — |
| SECONDARY Period 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
3.5; -0.4; 3.7; -6.2; 4.3; 0.9 | — |
| SECONDARY Period 2: Change From Baseline in SBP and DBP |
1.7; 1.3; 3.0; -0.5; -0.1; 0.6 | — |
| SECONDARY Period 3: Change From Baseline in SBP and DBP |
-0.1; -3.4; -3.3; 3.6; -1.4; -2.1 | — |
| SECONDARY Period 1: Change From Baseline in Pulse Rate |
-0.3; -1.3; 2.0; -1.6 | — |
| SECONDARY Period 2: Change From Baseline in Pulse Rate |
3.9; 5.4; 4.8; 4.2; 3.8; 2.7 | — |
| SECONDARY Period 3: Change From Baseline in Pulse Rate |
1.8; 2.2; 0.3; 3.1; 1.3; -2.1 | — |
| SECONDARY Period 1: Change From Baseline in Respiratory Rate |
-0.9; 0.3; -1.5; -0.8 | — |
| SECONDARY Period 2: Change From Baseline in Respiratory Rate |
-0.5; 0.4; -0.6; 1.3; -0.4; 0.1 | — |
| SECONDARY Period 3: Change From Baseline in Respiratory Rate |
1.4; 0.5; 0.3; -0.5; 0.6; 0.3 | — |
| SECONDARY Period 1: Change From Baseline in Body Temperature |
-0.04; -0.14; -0.19; 0.03 | — |
| SECONDARY Period 2: Change From Baseline in Body Temperature |
-0.14; -0.25; -0.19; -0.05; -0.13; -0.13 | — |
| SECONDARY Period 3: Change From Baseline in Body Temperature |
-0.08; -0.18; 0.02; 0.00; -0.03; 0.06 | — |
| SECONDARY Period 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count |
0.045; 0.232; 2.023; 0.512; 3.038; 270.2 | — |
| SECONDARY Period 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count |
0.039; 0.206; 1.869; 0.488; 2.878; 264.2 | — |
| SECONDARY Period 3: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count |
0.043; 0.046; 0.042; 0.206; 0.211; 0.171 | — |
| SECONDARY Period 1: Absolute Values for Hematology Parameter: Hemoglobin |
146.4 | — |
| SECONDARY Period 2: Absolute Values for Hematology Parameter: Hemoglobin |
146.5 | — |
| SECONDARY Period 3: Absolute Values for Hematology Parameter: Hemoglobin |
149.8; 147.1; 147.7 | — |
| SECONDARY Period 1: Absolute Values for Hematology Parameter: Hematocrit |
0.4419 | — |
| SECONDARY Period 2: Absolute Values for Hematology Parameter: Hematocrit |
0.4406 | — |
| SECONDARY Period 3: Absolute Values for Hematology Parameter: Hematocrit |
0.4441; 0.4357; 0.4364 | — |
| SECONDARY Period 1: Absolute Values for Hematology Parameter: Erythrocytes |
5.143 | — |
| SECONDARY Period 2: Absolute Values for Hematology Parameter: Erythrocytes |
5.179 | — |
| SECONDARY Period 3: Absolute Values for Hematology Parameter: Erythrocytes |
5.194; 5.099; 5.124 | — |
| SECONDARY Period 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume |
86.22 | — |
| SECONDARY Period 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume |
85.36 | — |
| SECONDARY Period 3: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume |
85.76; 85.72; 85.41 | — |
| SECONDARY Period 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin |
28.58 | — |
| SECONDARY Period 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin |
28.41 | — |
| SECONDARY Period 3: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin |
28.96; 28.96; 28.93 | — |
| SECONDARY Period 1: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen |
5.165; 4.456; 1.107; 9.2; 2.393; 30.5 | — |
| SECONDARY Period 2: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen |
4.916; 4.187; 1.194; 11.4; 2.406; 29.3 | — |
| SECONDARY Period 3: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen |
4.978; 5.018; 4.849; 4.283; 4.179; 4.157 | — |
| SECONDARY Period 1: Absolute Values for Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase |
101.3; 107.4; 21.0; 57.4; 16.6; 21.1 | — |
| SECONDARY Period 2: Absolute Values for Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase |
123.9; 116.5; 20.4; 59.3; 16.8; 20.3 | — |
| SECONDARY Period 3: Absolute Values for Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase |
110.3; 105.3; 100.3; 122.4; 115.6; 116.6 | — |
| SECONDARY Period 1: Absolute Values for Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin |
321.9; 90.28; 9.14; 1.87 | — |
| SECONDARY Period 2: Absolute Values for Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin |
314.8; 86.92; 9.41; 1.93 | — |
| SECONDARY Period 3: Absolute Values for Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin |
314.8; 299.3; 313.4; 94.82; 96.81; 88.91 | — |
| SECONDARY Period 1: Absolute Values for Chemistry Parameters: Albumin, Globulin, Protein |
44.1; 27.9; 71.9 | — |
| SECONDARY Period 2: Absolute Values for Chemistry Parameters: Albumin, Globulin, Protein |
44.9; 26.8; 71.8 | — |
| SECONDARY Period 3: Absolute Values for Chemistry Parameters: Albumin, Globulin, Protein |
45.9; 45.1; 45.3; 25.9; 27.8; 27.3 | — |
| SECONDARY Period 1: Absolute Values for Chemistry Parameters: Amylase, Lipase |
59.6; 22.4 | — |
| SECONDARY Period 2: Absolute Values for Chemistry Parameters: Amylase, Lipase |
56.8; 21.7 | — |
| SECONDARY Period 3: Absolute Values for Chemistry Parameters: Amylase, Lipase |
55.3; 56.9; 55.9; 26.4; 20.9; 21.8 | — |
| SECONDARY Period 1: Absolute Values for Urinalysis Parameter: Specific Gravity |
1.0181 | — |
| SECONDARY Period 2: Absolute Values for Urinalysis Parameter: Specific Gravity |
1.0176 | — |
| SECONDARY Period 3: Absolute Values for Urinalysis Parameter: Specific Gravity |
1.0179; 1.0169; 1.0160 | — |
| SECONDARY Period 1: Absolute Values for Urinalysis Parameter: Urobilinogen |
3.3860 | — |
| SECONDARY Period 2: Absolute Values for Urinalysis Parameter: Urobilinogen |
3.3860 | — |
| SECONDARY Period 3: Absolute Values for Urinalysis Parameter: Urobilinogen |
3.3860; 3.3860; 3.3860 | — |
| SECONDARY Period 1: Absolute Values for Urinalysis Parameter: pH |
5.88 | — |
| SECONDARY Period 2: Absolute Values for Urinalysis Parameter: pH |
6.00 | — |
| SECONDARY Period 3: Absolute Values for Urinalysis Parameter: pH |
6.03; 5.88; 6.16 | — |
| SECONDARY Period 1: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF, QTcB |
159.1; 161.3; 164.3; 160.9; 161.5; 95.2 | — |
| SECONDARY Period 2: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF, QTcB |
165.1; 165.4; 166.3; 165.0; 162.0; 94.1 | — |
| SECONDARY Period 3: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF, QTcB |
167.9; 164.1; 165.6; 166.9; 163.1; 164.6 | — |
| SECONDARY Period 1: Absolute Values for SBP and DBP |
118.8; 114.9; 119.0; 109.1; 76.1; 72.7 | — |
| SECONDARY Period 2: Absolute Values for SBP and DBP |
115.8; 115.3; 117.1; 113.6; 113.9; 114.6 | — |
| SECONDARY Period 3: Absolute Values for SBP and DBP |
115.8; 112.5; 112.6; 119.4; 114.4; 113.8 | — |
| SECONDARY Period 1: Absolute Values for Pulse Rate |
67.8; 66.8; 70.1; 66.4 | — |
| SECONDARY Period 2: Absolute Values for Pulse Rate |
68.3; 69.7; 69.1; 68.5; 68.1; 67.0 | — |
| SECONDARY Period 3: Absolute Values for Pulse Rate |
68.4; 68.9; 66.9; 69.8; 67.9; 64.6 | — |
| SECONDARY Period 1: Absolute Values for Respiratory Rate |
13.5; 14.6; 12.9; 13.6 | — |
| SECONDARY Period 2: Absolute Values for Respiratory Rate |
13.6; 14.5; 13.5; 15.3; 13.8; 14.3 | — |
| SECONDARY Period 3: Absolute Values for Respiratory Rate |
15.0; 14.1; 13.9; 13.1; 14.3; 13.9 | — |
| SECONDARY Period 1: Absolute Values for Body Temperature |
36.36; 36.26; 36.21; 36.43 | — |
| SECONDARY Period 2: Absolute Values for Body Temperature |
36.26; 36.15; 36.21; 36.35; 36.28; 36.28 | — |
| SECONDARY Period 3: Absolute Values for Body Temperature |
36.33; 36.22; 36.42; 36.40; 36.37; 36.46 | — |
| SECONDARY Period 2: Time of Maximum Observed Concentration (Tmax) of GSK3640254 for GSK3640254 Arm |
5.000 | — |
| SECONDARY Period 3: Tmax of GSK3640254 for Dolutegravir + GSK3640254 Arm |
5.000 | — |
| SECONDARY Period 2: Apparent Terminal Phase Half-life (T1/2) of GSK3640254 for GSK3640254 Arm |
NA | — |
| SECONDARY Period 3: T1/2 of GSK3640254 for Dolutegravir + GSK3640254 Arm |
23.417 | — |
| SECONDARY Period 1: Tmax of Dolutegravir for Dolutegravir Arm |
3.000 | — |
| SECONDARY Period 3: Tmax of Dolutegravir for Dolutegravir + GSK3640254 Arm |
3.000 | — |
| SECONDARY Period 1: T1/2 of Dolutegravir for Dolutegravir Arm |
14.492 | — |
| SECONDARY Period 3: T1/2 of Dolutegravir for Dolutegravir + GSK3640254 Arm |
14.690 | — |
Eligibility Criteria
Inclusion Criteria
- Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
- Subjects who are healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
- Body weight >=50 kilograms (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 31.0 kilograms per square meter (kg/m^2) (inclusive).
- Male or female subjects can participate. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP).
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
Exclusion Criteria
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A pre-existing condition interfering with normal gastrointestinal (GI) anatomy or motility (e.g., gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs or render the subject unable to take oral study intervention.
- Any history of significant underlying psychiatric disorder, including but not limited to schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
- Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment. Subjects with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy ( 1.5 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin 100 beats per minute [bpm] and females: 100 bpm); PR interval ( 200 milliseconds [msec]); QRS duration ( 110 msec); QTcF interval (males: >450 msec and females: >470 msec).
- History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units. One unit is equivalent to 8 grams of alcohol: a half-pint (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
- Regular use of tobacco- or nicotine-containing products within 3 months prior to Screening.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
Data sourced from ClinicalTrials.gov (NCT03816696). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.