Healthy subjects Not Applicable
Conditions
Interventions
This is a randomized, double-blind (sponsor open), placebo-controlled multiple ascending doses of combination K-757 and K833. Site staff and study participants were blinded to the treatment assignment
Sponsors
Kallyope (United States)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Understand the trial procedures and agree to participate by providing written informed consent 2. Be willing and able to comply with all trial procedures and restrictions 3. Be healthy between 18 to 55 years of age, inclusive, at the Screening Visit 4. Have a Body Mass Index (BMI) =19.0 and 45 years and with a minimum of 12 months of spontaneous amenorrhea with a Screening serum follicle-stimulating hormone level >30 mIU/mL). 7.3.2. Post hysterectomy, bilateral oophorectomy or bilateral salpingectomy, based on the subject’s recall of their medical history.
Exclusion criteria
Exclusion criteria: 1. Has participated in another investigational study within the following time period: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer or based on local regulations) before the Screening Visit. The window will be derived from the date of the last study procedure and/or AE related to the study procedure in the previous study to the Screening Visit of the current study. 2. Is an employee or immediate family member (e.g., spouse, parent, child, sibling) of the Sponsor or study site 3. Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerance to prescription or nonprescription drugs or food 4. Has a known hypersensitivity or contraindication to any component of K-757, K-833, related compounds or its excipients 5. Has a positive alcohol or drug screen at Screening or admission 6. Has a positive pregnancy test 7. Is a lactating/nursing female 8. Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency antibody, at the Screening Visit. Note: Subjects with positive hepatitis B virus or hepatitis C virus serology may be enrolled if quantitative polymerase chain reaction for hepatitis B virus or hepatitis C virus ribonucleic acid is negative. 9. Subject does not meet study site COVID-19 admission/study participation restrictions or has a fever (>38oC) 10. Had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks before the Screening Visit. 11. Is unable to refrain from the use of prescription or non-prescription drugs including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the first dose of study medication for each dosing period until two days after the last dose of study medication in each Panel, unless in the opinion of the Investigator and Kallyope Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Paracetamol (=2 grams [g] per day) and COVID vaccination are acceptable. 12. Has regular consumption of alcohol within 6 months before screening (>14 drinks/week where l drink= 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) or use of soft drugs (such as marijuana) within 3 months before Screening, or hard drugs (such as cocaine) within 6 months before Screening 13. Is unwilling or unable to refrain from study alcohol restrictions: Subjects will refrain from consuming alcohol from 7 days before the first and until the last PK blood sample has been collected and 7 days before the follow-up visit. At all other times, alcohol consumption is limited to no more than approximately 14 drinks/week where 1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor. 14. Is unable or unwilling to refrain from consumption of Seville oranges, grapefruit, grapefruit juice, pomelos, exotic citrus fruits, and grapefruit hybrids from 2 weeks before administration of the first dose of study drug, throughout the study, and until the Follow-up Visit 15. Unwilling to refrain from the mustard green family (eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, and mustard) or charbroiled meats beginning approximately 4
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety measures consisted of the collection of the following parameters: 1. Physical examination findings at screening, check-in, Day 13, and the 14-day post last dose follow-up visit 2. Vital signs collection of blood pressure, heart rate, and body temperature at Check in, Day 1 pre-dose, 2, and 6 h post dose; Days 3, 5, 8, and 11 pre-dose, Day 13 check-in; Day 14 pre-dose, 2, 6, and 24 h post-dose and the 14-day post last dose follow up visit. 3. 12-lead electrocardiograms (QTc) at Check in, Day 1 pre-dose, 2, and 6 h post dose; Days 3, 5, 8, and 11 pre-dose; Day 14 pre-dose, 2, 6, and 24 h post-dose 4. Blood chemistry and hematology at Check in, Day 1 8 and 24 h post-dose; Days 3, 5, 8, and 11 pre-dose; Day 13 check-in; Day14 pre-dose, 8, 24 h post-dose, and the 14-day post last dose follow up visit. 5. Collection of adverse events (AEs) following the signed information consent through the 14-day post last dose follow-up visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetics measured by plasma PK parameters of K-757 and K-833 including: AUC0-8, AUC0-last, Cmax, Tmax, t½, and volume of distribution (Vdss) and clearance (Cl). Timepoints included: 1.1. Day 1: 2 h pre-dose, 1, 2, 3, 4, 6, 8-, 12, 16, and 24-hours post-dose 1.2. Days 3, 5, 8, 11, 13 (pre-meal/predose) 1.3. Day 14: pre-dose, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 h post-dose 2. Pharmacodynamic measures consisted of plasma levels and changes from baseline of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP) and other PD biomarkers (if available). Timepoints included: 2.1. Day 1: 2 h pre-dose 1, 2, 3, 4, 6, 8, 11, 12, 14, 16, and 24 h post dose 2.2. Days 3, 5, 8, 11, 13 (pre-meal/predose) 2.3. Day 14: premeal/pre-dose, 1, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 h post-dose | — |
Countries
Northern Ireland, United Kingdom
Contacts
Public ContactAnnemarie Vance
Outcome results
None listed