A Phase 1, Randomized, Placebo-Controlled, First-in-Human, Single and Multiple Ascending Dose Study Designed to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered KT-621 in Healthy Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- KT-621
- Conditions
- Healthy Participants Study
- Sponsor
- Kymera Therapeutics, Inc.
- Enrollment
- 118
- Locations
- 1
- Primary Endpoint
- Treatment-emergent potentially clinically significant abnormalities in vital signs: heart rate (beats per minute)
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
This is a first-in-human study to evaluate safety, pharmacokinetics, and pharmacodynamics of single and multiple dose levels of KT-621 in healthy male and female adult participants.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants aged 19 to 55 years (inclusive) at the time of consent, with a weight of at least 50 kg if male or 40 kg if female, and a body mass index (BMI) between 18.0 and 30.0 kg/m² (inclusive) at Screening.
- •Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- •Participants must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Male participants (and their partners of childbearing potential) and female participants must agree to the contraception requirements as specified in the clinical protocol.
- •Female participants may not be pregnant, lactating, or breast-feeding or plan to become pregnant (including ova donation) within 30 days of last study drug administration.
- •Female participants must have a negative result for pregnancy test at Screening and on admission to the CRU.
Exclusion Criteria
- •Participants who have a clinically relevant history of respiratory, gastrointestinal (GI), renal, hepatic, hematological, lymphatic, endocrinological, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, ophthalmological, or connective tissue diseases or disorders.
- •Participants who have a clinically relevant surgical history (eg, surgery of the GI tract that could interfere with the PK of the trial medication) Note: prior appendectomy or cholecystectomy is not exclusionary.
- •Participants with a history of alcohol or substance abuse within the previous 5 years.
- •Participants who have any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.
- •Participants who test positive for alcohol and drugs of abuse at Screening and on admission to the CRU.
- •Participants who have acute GI symptoms at the time of Screening or admission to the CRU (eg, nausea, vomiting, diarrhea, heartburn).
- •Participants whose results from clinical laboratory safety tests are outside the local reference range at Screening and on admission to the CRU.
- •Participants who have previously received KT-621 in another cohort in this study.
- •Participants who have been dosed with any investigational drug or device in a clinical study within 30 days or 5 half-lives (whichever is longer) of KT-621/placebo administration.
Arms & Interventions
KT-621
Each participant receives either a single oral dose (SAD) or multiple oral doses (MAD) of KT-621.
Intervention: KT-621
Placebo
Each participant receives either a single oral dose (SAD) or multiple oral doses (MAD) of matched placebo.
Intervention: Placebo
Outcomes
Primary Outcomes
Treatment-emergent potentially clinically significant abnormalities in vital signs: heart rate (beats per minute)
Time Frame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Treatment-emergent potentially clinically significant abnormalities in vital signs: respiratory rate (breaths per minute)
Time Frame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Treatment-emergent potentially clinically significant abnormalities in vital signs: temperature (degrees Celsius)
Time Frame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Incidence of adverse events
Time Frame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Treatment-emergent potentially clinically-significant abnormalities in safety laboratory parameters: hematology
Time Frame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Hemoglobin, Hematocrit, Erythrocytes, Mean corpuscular volume, Platelets, Leukocytes, Eosinophils, Basophils Neutrophils Lymphocytes Monocytes
Treatment-emergent potentially clinically significant abnormalities in safety laboratory parameters: serum chemistry
Time Frame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Glucose, Blood urea nitrogen, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Phosphate, Bilirubin, total and direct, Alkaline phosphatase, Aspartate transaminase (=SGOT), Alanine transaminase (=SGPT), Gamma glutamyl transferase, Total protein, Albumin, Creatine kinase, HbA1c, Lactate dehydrogenase (LDH)
Treatment-emergent potentially clinically significant abnormalities in safety laboratory parameters: coagulation
Time Frame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Activated partial thromboplastin time, Prothrombin time, International Normalized Ratio, Fibrinogen
Treatment-emergent potentially clinically significant abnormalities in vital signs: blood pressure (mmHg)
Time Frame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Treatment-emergent potentially clinically significant abnormalities in electrocardiogram values: QTcF (milliseconds)
Time Frame: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Secondary Outcomes
- Maximum concentration (Cmax): observed maximum concentrations derived from plasma concentration data(Day 1 (SAD); Day 1, Day 7, and Day 14 (MAD))
- Time to maximum concentration (Tmax): observed time to achieve maximum concentrations derived from plasma concentration data(Day 1 (SAD); Day 1, Day 7, and Day 14 (MAD))
- Area under the curve (AUC0-last): Area under the plasma concentration-time curve calculated using non-compartmental analysis from time zero to the last observed timepoint(Day 1 (SAD); Day 1, Day 7, and Day 14 (MAD))
- Area under the curve (AUC0-infinity): Area under the plasma concentration-time curve calculated using non-compartmental analysis from time zero to infinite time(Day 1 (SAD))
- Area under the curve (AUC0-tau): Area under the plasma concentration-time curve calculated using non-compartmental analysis from time zero to end of the dosing interval(Day 1, Day 7, and Day 14 (MAD))
- Terminal elimination half-life (t1/2): elimination half-life calculated using non-compartmental analysis(Day 1 (SAD) and Day 14 (MAD))
- Fraction excreted: Fraction of drug excreted unchanged in urine(Day 14 (MAD))