None listed
Conditions
Brief summary
Around 12 participants will follow a fixed treatment plan to study how GV-100 interacts with other medicines. After screening, they will stay at the study site for about 2 weeks and return for a follow-up visit. They will first receive two medicines to check how their body processes them, then take GV-100 daily for 7 days. Later, the same medicines will be given again along with GV-100 to see if it changes how other drugs are handled in the body.
Interventions
The Drug-drug Interaction part will evaluate the effect of GV-100 on cytochrome (CYP) 3A4 and cytochrome (CYP) 2B6 activity and may be initiated after Safety Review Committee (SRC) approval of safety, tolerability, and Pharmacokinetic (PK) data from multiple ascending dose (MAD) Cohort 3. The GV-100 dose will be selected based on cumulative safety and Pharmacokinetic (PK) data.
Approximately 12 participants will be enrolled in a fixed-sequence, non-randomized, open-label design. Probe substrate
The Drug-drug Interaction part will evaluate the effect of GV-100 on cytochrome (CYP) 3A4 and cytochrome (CYP) 2B6 activity and may be initiated after Safety Review Committee (SRC) approval of safety, tolerability, and Pharmacokinetic (PK) data from multiple ascending dose (MAD) Cohort 3. The GV-100 dose will be selected based on cumulative safety and Pharmacokinetic (PK) data. Approximately 12 participants will be enrolled in a fixed-sequence, non-randomized, open-label design. Probe substrates will include midazolam 1 mg (cytochrome (CYP) 3A4 substrate) and bupropion 75milligram (cytochrome (CYP) 2B6 substrate), both administered orally. Participants will be screened between Day -28 and Day -2, admitted on Day -1, confined through Day 15, and return for follow-up on Day19 (±1 day). Participants will be administered a single oral dose of 1 mg midazolam, immediately followed by a single oral dose of 75 mg bupropion on Day 1. On Day 11, the participants will be administered a single oral dose of 1 mg midazolam, immediately followed by a single oral dose of 75 mg bupropion, immediately followed by a single oral dose of GV-100. Participants will be admitted to hospital as inpatient and the administration for the selected dose of GV-100QD for 7 consecutive days from Days 6 to 12. A mouth check will be performed following administration to confirm complete consumption of the IP.
Sponsors
Gilva Therapeutics, INC.
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
- Male or female participants, aged more than or equal 18 to less than or equal to 65 years at the time of providing informed consent, who are non-smokers (no use of tobacco or nicotine-containing products within 3 months prior to screening), with a body mass index (BMI) greater than 18.0 and less than 32.0kilogram/meter square, and a minimum body weight of 50.0 kilogram. - Healthy individuals, as determined by the Principal Investigator or delegate, defined as: a. No clinically significant illness or surgical procedures within 4 weeks prior to study drug administration. b. No clinically significant history of neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, or metabolic disorders. - Capable of understanding the study procedures and willing to provide written informed consent prior to participation.
Exclusion criteria
- Any clinically significant abnormal finding on physical examination, as determined by the PrincipalInvestigator or delegate. - Clinically significant abnormal laboratory results at screening, in the opinion of the Principal Investigatoror delegate. - Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and/or total bilirubin levels greaterthan 1.5 × the upper limit of normal (ULN) at screening. - Estimated glomerular filtration rate (eGFR) Less than or equal 90 milliliter/minute/1.73 meter square atscreening, calculated using the CKD-EPI equation. - Positive test results at screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen or antibody. Participants with a positive hepatitis B surface antibody (HBsAb) due to prior vaccination are permitted. - Any current active infection, including localized infections, or a recent history (within 1 week prior to dosing) of infection, cough, or fever, or a history of recurrent or chronic infections. - Any disease or history of surgery that, in the opinion of the Principal Investigator or delegate, couldsignificantly affect the absorption, distribution, metabolism, or excretion of the investigational product. - Positive pregnancy test or lactation in female participants. - Positive urine drug screen, urine cotinine test, or alcohol breath test. - History of clinically significant allergic reactions, including anaphylaxis, hypersensitivity, or angioedema,to any medication, or known allergy to GV-100, related compounds, or any formulation excipients. - Clinically significant abnormalities in Electrocardiogram findings or vital signs at screening, as determined by the Principal Investigator or delegate. - Supine systolic blood pressure greater than or equal to 160 mmHg or diastolic blood pressure greater than or equal to 95 millimeters of mercury. (mmHg) at screening after at least 5 minutes of rest. If elevated, blood pressure will be repeated two additional times, and the average of three measurements will be used to assess eligibility. - History of drug abuse within 6 months prior to first dosing, or substance abuse considered clinically significant by the Principal Investigator or delegate. - History of alcohol abuse within 6 months prior to first dosing, defined as consumption exceeding 21 units per week for males or 14 units per week for females (1 unit equals 240 milliliter beer, 120 milliliter wine, or 30 milliliter distilled Alcohol). - Use of depot injections or implants within 3 months prior to first dosing. - Receipt of live or live-attenuated vaccines (bacterial or viral) within 12 weeks prior to screening, orplanned receipt during the study period. - Receipt of any vaccine, including COVID-19 vaccines, within 14 days prior to first dosing. - Use of any drug known to induce or inhibit hepatic drug-metabolizing enzymes within 30 days or 5 half-lives (whichever is longer) prior to first dosing. - Use of prescription medications within 14 days or 5 half-lives (whichever is longer) prior to first dosing. - Use of over-the-counter medications or natural health products, including herbal remedies (e.g., St.John’s wort), traditional medicines, probiotics, dietary supplements, or sports supplements within 14 daysor 5 half-lives (whichever is longer) prior to first dosing, except for occasional paracetamol up to2grams/day. - Participation in another clinical research study involving an investigational or marketed drug ordevicewithin 30 days or 5 half-lives (whichever is longer) prior to first dosing; participation involving abiologicalproduct within 90 days prior to dosing; or concurrent participation in any investigational studywithout drugor device administration. - Donation of plasma or platelets within 14 days prior to dosing, or donation or loss of equals 500 milliliterofwhole blood within 60 days prior to dosing. - Previous exposure to GV-100. - Any other condition or circumstance that, in the opinion of the Principal Investigator or delegate, could interfere with study participation or compliance, which will be documented in the source records. - Psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or Columbia Suicidality Severity Rating Scale (C-SSRS) score above Type 1 ideation. - Use of monoamine oxidase inhibitors (MAOIs) (e.g., isocarboxazid, phenelzine, tranylcypromine, moclobemide) for 30 days (or 5 half-lives, whichever is longer) prior to first dosing. - History of glaucoma. - History of significant respiratory depression, airway obstruction, oxygen desaturation, or apnea. - History of anorexia nervosa or bulimia. - History of seizure disorders. - History of anaphylactoid/anaphylactic reactions or Stevens-Johnson syndrome. - Any known allergic reactions to midazolam or other related drugs, or to any excipient in the formulation including allergies to cherries. - Any known allergic reactions to bupropion or other related drugs, or to any excipient in the formulation.
Outcome results
None listed