Clinical trial NCT04617509: A Study in Healthy Subjects to Evaluate Pharmacokinetics and Food Effect After Dosing of GS-248
Official title: An Open, One-sequence, Three-period Study in Healthy Subjects to Evaluate Pharmacokinetics and Food Effect After Oral Single Dosing of Two Different Solid Formulations of GS-248
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetic
Keywords: Pharmacokinetic
Lead sponsor: Gesynta Pharma AB
Sponsor class: INDUSTRY
Collaborators: name: CTC Clinical Trial Consultants AB
name: Research Institutes of Sweden
First posted: 2020-11-05
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study is divided in two parts. Part I will evaluate PK, safety and tolerability of a single oral dose of two different formulations of GS-248 in fasting conditions. Part II will evaluate PK, safety and tolerability of one of the two different formulations of GS-248 in fed conditions. Subjects are expected to participate in both Part I and Part II.
Primary purpose: TREATMENT

Brief summary: The study will collect information about pharmacokinetics (PK), safety and tolerability following a single dose of GS-248 in two different oral solid formulations in capsules to healthy subjects. It will also collect information about pharmacokinetics (PK), safety and tolerability following a single dose of one of the two formulations of GS-248 in fed condition.

Detailed description: The study is divided in two parts. Part I will evaluate PK, safety and tolerability of a single oral dose of two different formulations of GS-248 in fasting conditions. Part II will evaluate PK, safety and tolerability of one of the two different formulations of GS-248 in fed conditions.

In Part I, a single oral dose of GS-248 in two different solid formulations will be administered to 14 healthy subjects. All subjects will first receive Formulation A and then Formulation B. A wash-out period of at least 4 days will be applied between the IMP administrations. Both doses contain 120 mg GS 248. For Part I, subjects will come to the clinic for single dose administration of Formulation A or Formulation B, respectively, and PK and safety assessments. Safety assessments include AE reporting, physical examination, ECG, vital signs, body temperature, and blood sampling for analysis of safety laboratory parameters.

After evaluation of the PK profiles of Formulation A and B in Part I of the study, one formulation will be selected to be given following intake of a standardised breakfast in Part II of the study. Subjects will return to the clinic for a second dose of the selected formulation, yet now in fed conditions. The assessments during fed conditions will be the same as during fasting conditions except that the subjects will consume a high-fat high-calorie breakfast 30 minutes prior to IMP administration.

Eligibility criteria: Inclusion Criteria:

1. Willing and able to give written informed consent for participation in the study.
2. Healthy male or female subject aged ≥ 18 and ≤70 years.
3. Body Mass Index (BMI) ≥ 19.0 and ≤ 30.0 kg/m2.
4. Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
5. Women of child bearing potential (WOCBP) must practice abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the subject) or must agree to use a highly effective method of contraception with a failure rate of \< 1% to prevent pregnancy (combined \[oestrogen and progestogen containing\] hormonal contraception \[oral, intravaginal, transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, implantable\], intrauterine device \[IUD\]or intrauterine hormone-releasing system \[IUS\]) from at least 4 weeks prior to dose to 4 weeks after last dose.

Exclusion Criteria:

1. Known allergy to GS-248.
2. Females who are breast feeding or who plan to become pregnant until 2 weeks after the end-of-study visit.
3. Positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) at screening and within 24 h prior to the first administration of IMP.
4. Regular use of corticosteroids (inhaled and systemic), NSAIDs, aspirin or coxibs, antacids, PPIs, or any other medication that changes gastric pH within 14 days of study drug administration.
5. Regular use of any prescribed or non-prescribed medication including analgesics, herbal remedies, vitamins and minerals within 2 weeks prior to the (first) administration of IMP, except hormonal contraception and occasional intake of paracetamol (maximum 2000 mg/day; and not exceeding 3000 mg/week) and nasal decongestants without cortisone, antihistamine or anticholinergics for a maximum of 10 days, at the discretion of the Investigator.
6. Presence of inherited or acquired disorders of platelet function, bleeding or coagulation, as judged by the investigator.
7. History or presence of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
8. After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges:

   * Systolic blood pressure \<90 or \>140 mmHg, or
   * Diastolic blood pressure \<50 or \>90 mmHg, or
   * Pulse \<40 or \>90 bpm
9. Positive test for serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb) or HIV 1 and/or 2 antibodies at screening.
10. Presence or history of drug and/or alcohol abuse and/or excessive intake of alcohol and/or history, or current use, of anabolic steroids, as judged by the Investigator.
11. Positive test for drugs of abuse or alcohol at screening or on admission to the unit prior to administration of the IMP.
12. Participation in other interventional studies within 3 months prior to administration of study drug.
13. Consumption of grapefruit, grapefruit juice, other grapefruit-containing products, or Seville oranges within 14 days of first IMP administration.
14. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
15. Malignancy within the past 5 years with the exception of in situ removal of basal cell carcinoma.
16. Any planned major surgery within the duration of the study.
17. Prolonged QTcF (\>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG, as judged by the Investigator.
18. Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than three times per week is allowed before screening visit.
19. Regular excessive caffeine consumption defined by a daily intake of \>5 cups of caffeine-containing beverages.
20. Intake of xanthine- and/or taurine-containing energy drinks within 2 days prior to screening and prior to IMP administration.
21. Plasma donation within one month of screening or blood donation (or corresponding blood loss) during three months prior to screening.
22. Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.
23. Estimated glomerular filtration rate (eGFR) \< 50 mL/min/1.73 m2 (determined by the revised Lund-Malmö GFR estimating equation).
24. Subjects with swallowing disorders, which may affect the subject´s capability to swallow the IMP.
25. Subjects who are vegetarian or for other reasons cannot eat the high-fat high-calorie breakfast.

Primary outcomes:
measure: Cmax
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)
measure: AUC0-inf
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)
measure: AUC0-24h
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)
measure: Tmax
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)
measure: T1/2(z)
timeFrame: T1/2 (z) was assessed for the terminal elimination phase up to 48 hours
measure: Vz/F
timeFrame: Vz/F was assessed for the terminal elimination phase up to 48 hours.
measure: CL/F
timeFrame: CL/F was assessed for a single dose of GS-248 up to 48 hours.
Secondary outcomes:
measure: Number of Treatment Related Adverse Events
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.
measure: Number of Clinically Significant (CS) Changes in Physical Examination
timeFrame: Physical examination was performed at pre-defined timepoints from the Screening Visit until the End-of- Study Visit i.e. Visit 7, day 3, up to 30 days.
measure: Number of Clinically Significant (CS) Changes in Vital Signs
timeFrame: Vital signs ware assessed at pre-defined timepoints from the Screening Visit until the End-of- Study Visit i.e. Visit 7, day 3, up to 30 days.
measure: Number of Clinically Significant (CS) Changes in Resting 12-lead Electrocardiogram (ECG)
timeFrame: ECG evaluation was assessed at pre-defined timepoints from the Screening Visit until the End-of- Study Visit i.e. Visit 7, day 3, up to 30 days.
measure: Number of Clinically Significant (CS) Changes in Safety Laboratory Parameters
timeFrame: Blood samples were collected at pre-defined timepoints from the Screening Visit until the End-of- Study Visit i.e. Visit 7, day 3, up to 30 days.
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Clinical Trial Consultants AB
Study officials:
affiliation: CTC Clinical Trial Consultants AB
name: Helena Litorp, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: