Trial Outcomes & Findings for A Study in Healthy Subjects to Evaluate Pharmacokinetics and Food Effect After Dosing of GS-248 (NCT NCT04617509)

Results Overview

The Maximal Plasma Concentration (Cmax) after a single dose of Formulation A and B of GS 248 respectively in fasting conditions and after a single dose of Formulation A of GS-248 in fed condition. Blood samples for bioanalysis of GS-248 and subsequent PK analysis were collected as venous blood samples.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

From time 0 (time of dosing) to 48 hours after dose (concentration measured at timepoints pre-dose and 0:15, 0:30, 1, 1:30, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Results posted on

2021-08-31

Participant Flow

The subjects were recruited from CTC's database of healthy volunteers and from advertising in media (including social media). Screening visits were performed at CTC research clinic. Recruitment period started 24MAR2020 (the day after approval received from IEC and CA) and lasted until 06APR2020 (date for last subject screened).

Screening (Visit 1) took place from Day -28 to Day -1 and included an eligibility check and a general health assessment. A total of 29 subjects were screened for participation. Eleven subjects were screening failures and 4 subjects were reserves who were not used in the study. Fourteen subjects were included and dosed in the study.

Participant milestones

Participant milestones
Measure	Part I GS-248 Formulation A Formulation A given in fasting state. Formulation A GS-248: Formulation A of GS-248 in a lipid-based size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part I GS-248 Formulation B Formulation B given in fasting state. Formulation B GS-248: Formulation B of GS-248 in a dry powder size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part II GS-248 Formulation A in Fed Condition Formulation A given in fed condition. Formulation A was selected for the Food Interaction Part of the study, based on the PK profiles of both Formulation A and B. Formulation A of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg.
Period 1: Part 1 Formulation A STARTED	14	0	0
Period 1: Part 1 Formulation A COMPLETED	14	0	0
Period 1: Part 1 Formulation A NOT COMPLETED	0	0	0
Period 2: Part 1 Formulation B STARTED	0	14	0
Period 2: Part 1 Formulation B COMPLETED	0	14	0
Period 2: Part 1 Formulation B NOT COMPLETED	0	0	0
Period 3: Part 2 Formulation A Fed Cond. STARTED	0	0	14
Period 3: Part 2 Formulation A Fed Cond. COMPLETED	0	0	13
Period 3: Part 2 Formulation A Fed Cond. NOT COMPLETED	0	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study in Healthy Subjects to Evaluate Pharmacokinetics and Food Effect After Dosing of GS-248

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Trial n=14 Participants All subjects who were included in the study i.e. randomized in Part I GS-248 Formulation A.
Age, Continuous	44.3 years STANDARD_DEVIATION 17.1 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Sweden	14 participants n=5 Participants
Height	171.6 cm STANDARD_DEVIATION 10.8 • n=5 Participants
Weight	74.5 kg STANDARD_DEVIATION 17.14 • n=5 Participants
BMI	25.1 kg/m^2 STANDARD_DEVIATION 3.7 • n=5 Participants

PRIMARY outcome

Timeframe: From time 0 (time of dosing) to 48 hours after dose (concentration measured at timepoints pre-dose and 0:15, 0:30, 1, 1:30, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Population: Part I Formulation A: Data based on Formulation PK analysis set i.e. 14 subjects. Part I Formulation B: Data based on Formulation PK analysis set i.e. 14 subjects. Part II Formulation A fed: Data based on Formulation PK analysis set i.e. 13 subjects. Part II Formulation A fasting (partial set): Data based on Formulation PK analysis set i.e. 13 subjects.

The Maximal Plasma Concentration (Cmax) after a single dose of Formulation A and B of GS 248 respectively in fasting conditions and after a single dose of Formulation A of GS-248 in fed condition. Blood samples for bioanalysis of GS-248 and subsequent PK analysis were collected as venous blood samples.

Outcome measures

Outcome measures
Measure	Part I GS-248 Formulation A n=14 Participants Formulation A given in fasting state. Formulation A GS-248: Formulation A of GS-248 in a lipid-based size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part I GS-248 Formulation B n=14 Participants Formulation B given in fasting state. Formulation B GS-248: Formulation B of GS-248 in a dry powder size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part II GS-248 Formulation A in Fed Condition n=13 Participants Formulation A given in fed condition. Formulation A was selected for the Food Interaction Part of the study, based on the PK profiles of both Formulation A and B. Formulation A of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg with breakfast.	Part II GS-248 Formulation A in Fasting Condition (Partial Set) n=13 Participants This arm (subject analysis set) was used for a comparison of PK parameters between Formulation A under fed and fasted conditions (namely calculation of the relative bioavailability). The analysis set is part of the Food Interaction PK Analysis Set (PKAS - Food Interaction), and consisted of all subjects in Arm 1 (receiving Formulation A under fasted conditions) who, subsequently, also received Formulation A under fed conditions in the third treatment period of the study (Arm 3). Since 1 subject terminated the study prematurely between study treatment period 1 and 3, only 13 subjects were included in this analysis set that was used for the assessment of the relative bioavailability of Formulation A in fed versus fasted conditions.
Cmax	508.6 nmol/L Standard Deviation 220.9	384.5 nmol/L Standard Deviation 219.1	289.5 nmol/L Standard Deviation 184.4	499.5 nmol/L Standard Deviation 227.2

PRIMARY outcome

Timeframe: From time 0 (time of dosing) to 48 hours after dose (concentration measured at timepoints pre-dose and 0:15, 0:30, 1, 1:30, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Population: Part I Formulation A: Data based on Formulation PK analysis set i.e. 14 subjects. Part I Formulation B: Data based on Formulation PK analysis set i.e. 14 subjects. Part II Formulation A fed: Data based on Formulation PK analysis set i.e. 13 subjects. Part II Formulation A fasting (partial set): Data based on Formulation PK analysis set i.e. 13 subjects.

The Area Under the Curve (AUC) for the time interval 0-infinity of GS-248 after a single dose of Formulation A and B of GS 248 respectively in fasting conditions and after a single dose of Formulation A of GS-248 in fed condition. The mean AUC of GS-248 was assessed by means of non-compartmental analysis (NCA). Blood samples for bioanalysis of GS-248 and subsequent PK analysis were collected as venous blood samples.

Outcome measures

Outcome measures
Measure	Part I GS-248 Formulation A n=14 Participants Formulation A given in fasting state. Formulation A GS-248: Formulation A of GS-248 in a lipid-based size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part I GS-248 Formulation B n=14 Participants Formulation B given in fasting state. Formulation B GS-248: Formulation B of GS-248 in a dry powder size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part II GS-248 Formulation A in Fed Condition n=13 Participants Formulation A given in fed condition. Formulation A was selected for the Food Interaction Part of the study, based on the PK profiles of both Formulation A and B. Formulation A of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg with breakfast.	Part II GS-248 Formulation A in Fasting Condition (Partial Set) n=13 Participants This arm (subject analysis set) was used for a comparison of PK parameters between Formulation A under fed and fasted conditions (namely calculation of the relative bioavailability). The analysis set is part of the Food Interaction PK Analysis Set (PKAS - Food Interaction), and consisted of all subjects in Arm 1 (receiving Formulation A under fasted conditions) who, subsequently, also received Formulation A under fed conditions in the third treatment period of the study (Arm 3). Since 1 subject terminated the study prematurely between study treatment period 1 and 3, only 13 subjects were included in this analysis set that was used for the assessment of the relative bioavailability of Formulation A in fed versus fasted conditions.
AUC0-inf	1491 h*nmol/L Standard Deviation 478.1	1182 h*nmol/L Standard Deviation 567.4	1119 h*nmol/L Standard Deviation 463.9	1494 h*nmol/L Standard Deviation 497.4

PRIMARY outcome

Timeframe: From time 0 (time of dosing) to 24 hours after dose (concentration measured at timepoints pre-dose and 0:15, 0:30, 1, 1:30, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Population: Part I Formulation A: Data based on Formulation PK analysis set i.e. 14 subjects. Part I Formulation B: Data based on Formulation PK analysis set i.e. 14 subjects. Part II Formulation A fed: Data based on Formulation PK analysis set i.e. 13 subjects. Part II Formulation A fasting (partial set): Data based on Formulation PK analysis set i.e. 13 subjects.

The Area Under the Curve (AUC) for the time interval 0-24h of GS-248 after a single dose of Formulation A and B of GS 248 respectively in fasting conditions and after a single dose of Formulation A of GS-248 in fed condition. The mean AUC of GS-248 for the time interval 0-24 h was assessed by means of non-compartmental analysis (NCA). Blood samples for bioanalysis of GS-248 and subsequent PK analysis were collected as venous blood samples.

Outcome measures

Outcome measures
Measure	Part I GS-248 Formulation A n=14 Participants Formulation A given in fasting state. Formulation A GS-248: Formulation A of GS-248 in a lipid-based size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part I GS-248 Formulation B n=14 Participants Formulation B given in fasting state. Formulation B GS-248: Formulation B of GS-248 in a dry powder size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part II GS-248 Formulation A in Fed Condition n=13 Participants Formulation A given in fed condition. Formulation A was selected for the Food Interaction Part of the study, based on the PK profiles of both Formulation A and B. Formulation A of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg with breakfast.	Part II GS-248 Formulation A in Fasting Condition (Partial Set) n=13 Participants This arm (subject analysis set) was used for a comparison of PK parameters between Formulation A under fed and fasted conditions (namely calculation of the relative bioavailability). The analysis set is part of the Food Interaction PK Analysis Set (PKAS - Food Interaction), and consisted of all subjects in Arm 1 (receiving Formulation A under fasted conditions) who, subsequently, also received Formulation A under fed conditions in the third treatment period of the study (Arm 3). Since 1 subject terminated the study prematurely between study treatment period 1 and 3, only 13 subjects were included in this analysis set that was used for the assessment of the relative bioavailability of Formulation A in fed versus fasted conditions.
AUC0-24h	1420 h*nmol/L Standard Deviation 459.4	1104 h*nmol/L Standard Deviation 527.2	1014 h*nmol/L Standard Deviation 377.6	1419 h*nmol/L Standard Deviation 478.2

PRIMARY outcome

Timeframe: From time 0 (time of dosing) to 48 hours after dose (concentration measured at timepoints pre-dose and 0:15, 0:30, 1, 1:30, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Population: Part I Formulation A: Data based on Formulation PK analysis set i.e. 14 subjects. Part I Formulation B: Data based on Formulation PK analysis set i.e. 14 subjects. Part II Formulation A fed: Data based on Formulation PK analysis set i.e. 13 subjects. Part II Formulation A fasting (partial set): Data based on Formulation PK analysis set i.e. 13 subjects.

Time to Cmax (Tmax) after a single dose of Formulation A and B of GS 248 respectively in fasting conditions and after a single dose of Formulation A of GS-248 in fed condition. Blood samples for bioanalysis of GS-248 and subsequent PK analysis were collected as venous blood samples.

Outcome measures

Outcome measures
Measure	Part I GS-248 Formulation A n=14 Participants Formulation A given in fasting state. Formulation A GS-248: Formulation A of GS-248 in a lipid-based size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part I GS-248 Formulation B n=14 Participants Formulation B given in fasting state. Formulation B GS-248: Formulation B of GS-248 in a dry powder size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part II GS-248 Formulation A in Fed Condition n=13 Participants Formulation A given in fed condition. Formulation A was selected for the Food Interaction Part of the study, based on the PK profiles of both Formulation A and B. Formulation A of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg with breakfast.	Part II GS-248 Formulation A in Fasting Condition (Partial Set) n=13 Participants This arm (subject analysis set) was used for a comparison of PK parameters between Formulation A under fed and fasted conditions (namely calculation of the relative bioavailability). The analysis set is part of the Food Interaction PK Analysis Set (PKAS - Food Interaction), and consisted of all subjects in Arm 1 (receiving Formulation A under fasted conditions) who, subsequently, also received Formulation A under fed conditions in the third treatment period of the study (Arm 3). Since 1 subject terminated the study prematurely between study treatment period 1 and 3, only 13 subjects were included in this analysis set that was used for the assessment of the relative bioavailability of Formulation A in fed versus fasted conditions.
Tmax	1.500 hours Interval 1.0 to 3.0	1.500 hours Interval 1.0 to 3.03	3.000 hours Interval 1.0 to 4.03	1.500 hours Interval 1.0 to 3.0

PRIMARY outcome

Timeframe: T1/2 (z) was assessed for the terminal elimination phase up to 48 hours

Population: Part I Formulation A: Data based on Formulation PK analysis set i.e. 14 subjects. Part I Formulation B: Data based on Formulation PK analysis set i.e. 14 subjects. Part II Formulation A fed: Data based on Formulation PK analysis set i.e. 13 subjects. Part II Formulation A fasting (partial set): Data based on Formulation PK analysis set i.e. 13 subjects.

Plasma half-life associated with the terminal elimination phase (T1/2(z)) after a single dose of Formulation A and B of GS 248 respectively in fasting conditions and after a single dose of Formulation A of GS-248 in fed condition. Blood samples for bioanalysis of GS-248 and subsequent PK analysis were collected as venous blood samples.

Outcome measures

Outcome measures
Measure	Part I GS-248 Formulation A n=14 Participants Formulation A given in fasting state. Formulation A GS-248: Formulation A of GS-248 in a lipid-based size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part I GS-248 Formulation B n=14 Participants Formulation B given in fasting state. Formulation B GS-248: Formulation B of GS-248 in a dry powder size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part II GS-248 Formulation A in Fed Condition n=13 Participants Formulation A given in fed condition. Formulation A was selected for the Food Interaction Part of the study, based on the PK profiles of both Formulation A and B. Formulation A of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg with breakfast.	Part II GS-248 Formulation A in Fasting Condition (Partial Set) n=13 Participants This arm (subject analysis set) was used for a comparison of PK parameters between Formulation A under fed and fasted conditions (namely calculation of the relative bioavailability). The analysis set is part of the Food Interaction PK Analysis Set (PKAS - Food Interaction), and consisted of all subjects in Arm 1 (receiving Formulation A under fasted conditions) who, subsequently, also received Formulation A under fed conditions in the third treatment period of the study (Arm 3). Since 1 subject terminated the study prematurely between study treatment period 1 and 3, only 13 subjects were included in this analysis set that was used for the assessment of the relative bioavailability of Formulation A in fed versus fasted conditions.
T1/2(z)	10.69 hours Standard Deviation 2.912	16.09 hours Standard Deviation 15.26	13.36 hours Standard Deviation 9.914	10.91 hours Standard Deviation 2.902

PRIMARY outcome

Timeframe: Vz/F was assessed for the terminal elimination phase up to 48 hours.

Population: Part I Formulation A: Data based on Formulation PK analysis set i.e. 14 subjects. Part I Formulation B: Data based on Formulation PK analysis set i.e. 14 subjects. Part II Formulation A fed: Data based on Formulation PK analysis set i.e. 13 subjects. Part II Formulation A fasting (partial set): Data based on Formulation PK analysis set i.e. 13 subjects.

The mean volume of distribution (Vz/F) after a single dose of Formulation A and B of GS 248 respectively in fasting conditions and after a single dose of Formulation A of GS-248 in fed condition. Blood samples for bioanalysis of GS-248 and subsequent PK analysis were collected as venous blood samples.

Outcome measures

Outcome measures
Measure	Part I GS-248 Formulation A n=14 Participants Formulation A given in fasting state. Formulation A GS-248: Formulation A of GS-248 in a lipid-based size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part I GS-248 Formulation B n=14 Participants Formulation B given in fasting state. Formulation B GS-248: Formulation B of GS-248 in a dry powder size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part II GS-248 Formulation A in Fed Condition n=13 Participants Formulation A given in fed condition. Formulation A was selected for the Food Interaction Part of the study, based on the PK profiles of both Formulation A and B. Formulation A of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg with breakfast.	Part II GS-248 Formulation A in Fasting Condition (Partial Set) n=13 Participants This arm (subject analysis set) was used for a comparison of PK parameters between Formulation A under fed and fasted conditions (namely calculation of the relative bioavailability). The analysis set is part of the Food Interaction PK Analysis Set (PKAS - Food Interaction), and consisted of all subjects in Arm 1 (receiving Formulation A under fasted conditions) who, subsequently, also received Formulation A under fed conditions in the third treatment period of the study (Arm 3). Since 1 subject terminated the study prematurely between study treatment period 1 and 3, only 13 subjects were included in this analysis set that was used for the assessment of the relative bioavailability of Formulation A in fed versus fasted conditions.
Vz/F	2071 L Standard Deviation 1035	3884 L Standard Deviation 2940	3110 L Standard Deviation 1588	2125 L Standard Deviation 1057

PRIMARY outcome

Timeframe: CL/F was assessed for a single dose of GS-248 up to 48 hours.

Population: Part I Formulation A: Data based on Formulation PK analysis set i.e. 14 subjects. Part I Formulation B: Data based on Formulation PK analysis set i.e. 14 subjects. Part II Formulation A fed: Data based on Formulation PK analysis set i.e. 13 subjects. Part II Formulation A fasting (partial set): Data based on Formulation PK analysis set i.e. 13 subjects.

The mean total clearance (CL/F) after a single dose of Formulation A and B of GS 248 respectively in fasting conditions and after a single dose of Formulation A of GS-248 in fed condition. The mean total clearance (CL/F) was calculated by non-compartmental analysis (NCA). Blood samples for bioanalysis of GS-248 and subsequent PK analysis were collected as venous blood samples.

Outcome measures

Outcome measures
Measure	Part I GS-248 Formulation A n=14 Participants Formulation A given in fasting state. Formulation A GS-248: Formulation A of GS-248 in a lipid-based size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part I GS-248 Formulation B n=14 Participants Formulation B given in fasting state. Formulation B GS-248: Formulation B of GS-248 in a dry powder size 1 capsules, dose 120 mg given as a single-dose of 3 capsules a´40 mg.	Part II GS-248 Formulation A in Fed Condition n=13 Participants Formulation A given in fed condition. Formulation A was selected for the Food Interaction Part of the study, based on the PK profiles of both Formulation A and B. Formulation A of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg with breakfast.	Part II GS-248 Formulation A in Fasting Condition (Partial Set) n=13 Participants This arm (subject analysis set) was used for a comparison of PK parameters between Formulation A under fed and fasted conditions (namely calculation of the relative bioavailability). The analysis set is part of the Food Interaction PK Analysis Set (PKAS - Food Interaction), and consisted of all subjects in Arm 1 (receiving Formulation A under fasted conditions) who, subsequently, also received Formulation A under fed conditions in the third treatment period of the study (Arm 3). Since 1 subject terminated the study prematurely between study treatment period 1 and 3, only 13 subjects were included in this analysis set that was used for the assessment of the relative bioavailability of Formulation A in fed versus fasted conditions.
CL/F	132.9 L/h Standard Deviation 50.59	191.4 L/h Standard Deviation 105.0	185.2 L/h Standard Deviation 76.08	133.7 L/h Standard Deviation 52.56

SECONDARY outcome

Timeframe: AEs (including serious AEs [SAEs]) were collected from the start of IMP application in Part I until the end-of- study visit i.e. Visit 7, day 3, up to 30 days.