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

NCT04617509 | Completed Phase 1 Results

• 1 other identifier: GS-1002
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetic

Keywords

Pharmacokinetic

Outcome Measures

Primary Outcomes (7)

• Cmax

  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.

  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)

• AUC0-inf

  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.

  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)

• AUC0-24h

  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.

  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)

• Tmax

  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.

  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)

• T1/2(z)

  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.

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

• Vz/F

  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.

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

• CL/F

  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.

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

Secondary Outcomes (5)

• Number of Treatment Related Adverse Events

  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.

• Number of Clinically Significant (CS) Changes in Physical Examination

  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.

• Number of Clinically Significant (CS) Changes in Vital Signs

  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.

• Number of Clinically Significant (CS) Changes in Resting 12-lead Electrocardiogram (ECG)

  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.

• Number of Clinically Significant (CS) Changes in Safety Laboratory Parameters

  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.

Study Arms (3)

Part I GS-248 Formulation A

EXPERIMENTAL

Formulation A given in fasting state.

Drug: Formulation A GS-248

Part I GS-248 Formulation B

ACTIVE COMPARATOR

Formulation B given in fasting state.

Drug: Formulation B GS-248

Part II GS-248 Formulation A or B

OTHER

Formulation A or B given in fed condition

Drug: Formulation A GS-248; Drug: Formulation B GS-248

Interventions

Formulation A GS-248 DRUG

Formulation A of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg.

Part I GS-248 Formulation A; Part II GS-248 Formulation A or B

Formulation B GS-248 DRUG

Formulation B of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg.

Part I GS-248 Formulation B; Part II GS-248 Formulation A or B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give written informed consent for participation in the study.
• Healthy male or female subject aged ≥ 18 and ≤70 years.
• Body Mass Index (BMI) ≥ 19.0 and ≤ 30.0 kg/m2.
• Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
• 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.

You may not qualify if:

• Known allergy to GS-248.
• Females who are breast feeding or who plan to become pregnant until 2 weeks after the end-of-study visit.
• 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.
• 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.
• 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.
• Presence of inherited or acquired disorders of platelet function, bleeding or coagulation, as judged by the investigator.
• 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.
• 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
• Positive test for serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb) or HIV 1 and/or 2 antibodies at screening.
• 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.
• Positive test for drugs of abuse or alcohol at screening or on admission to the unit prior to administration of the IMP.
• Participation in other interventional studies within 3 months prior to administration of study drug.

Sponsors & Collaborators

• Gesynta Pharma AB: lead
• CTC Clinical Trial Consultants AB: collaborator
• Research Institutes of Sweden: collaborator

Study Sites (1)

Clinical Trial Consultants AB

Uppsala, 75237, Sweden

Location

Results Point of Contact

• Title: Charlotte Edenius
• Organization: Gesynta Pharma AB

charlotte.edenius@gesynta.se

+46733864246

Study Officials

• Helena Litorp, MD, PhD

  CTC Clinical Trial Consultants AB

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 27, 2020
• First Posted: November 5, 2020
• Study Start: March 31, 2020
• Primary Completion: May 27, 2020
• Study Completion: May 27, 2020
• Last Updated: August 31, 2021
• Results First Posted: August 31, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)