Study on the Effect of Famotidine on Pharmacokinetics of Taletrectinib

Official title

An Open-label, Fixed Sequence Study to Evaluate the Effect of Famotidine on the Pharmacokinetics and Safety of Taletrectinib in Healthy Adult Participant

Overview

This Phase 1 open-label trial aims to evaluate the effect of famotidine on the pharmacokinetics (PK), safety and tolerability of taletrectinib in healthy adult participants. To assess famotidine's impact on key PK parameters of taletrectinib and evaluate other PK parameters as well as safety endpoints. The study design: Part 1: Taletrectinib 600 mg administered under 2-hour fasting condition with three regimens: (Treatment A: Taletrectinib alone, Treatment B: Taletrectinib 2 h after single 40 mg famotidine. Treatment C: Taletrectinib dosed between two 20 mg famotidine doses). Part 2: Taletrectinib 400 mg administered with standard low-fat meal, followed by either Treatment B or C of famotidine co-administration.

Detailed description

Part 1 (taletrectinib 600 mg, 2-hour fast):

Treatment A: taletrectinib 600 mg administered 2 hours after a standard low-fat meal(Period 1).

Treatment B: taletrectinib 600 mg administered 2 hours after famotidine 40 mg given with a standard low-fat meal (Period 2).

Treatment C: taletrectinib 600 mg administered 10 hours after the first 20-mg famotidine dose, 2 hours after a standard low-fat meal, and 2 hours before the second 20-mg famotidine dose (Period 3).

Part 2 (taletrectinib 400 mg with a standard low-fat meal):

Treatment A: taletrectinib 400 mg within 30 min and no longer than 1 hour after a standard low-fat meal (Period 1).

Followed by either Treatment B or Treatment C Treatment B: taletrectinib 400 mg administered within 30 min and no longer than 1 hour after a standard low-fat meal and 2 hours after famotidine 40 mg (Period 2/Treatment B). Treatment C: taletrectinib 400 mg administered within 30 min and no longer than 1 hour after a standard low-fat meal, 10 hours after the first 20-mg famotidine dose, and 2 hours before the second 20-mg famotidine dose (Period 2/Treatment C).

Interventions

• Drug Taletrectinib
  A single oral dose of taletrectinib 600 mg 2 hours after a meal (2-hour fast),on the morning of Part 1, Treatment A Day 1.
• Drug Taletrectinib, Famotidine
  A single oral dose of famotidine 40mg administered with a meal on the morning of Part 1, Treatment B Day 1, and taletrectinib 600mg administered orally 2 hours later (2-hour fast).
• Drug Taletrectinib, Famotidine
  A single oral dose of famotidine 20mg administered to each participant on the night of Day 1. On the morning of Day 2, 8 hours after the prior dose of famotidine, participants will eat a meal and then be administered taletrectinib 600mg after a 2-hour fast; a final single oral dose of famotidine 20mg will be administered 2 hours after the dose of taletrectinib.
• Drug Taletrectinib
  A single oral dose of taletrectinib 400 mg dosed within 30 min (no longer than 1 hour) after a meal, on the morning of Part 2 Treatment A Day 1.
• Drug Taletrectinib, Famotidine
  A single oral dose of 40 mg famotidine and 2 hours later, taletrectinib 400 mg will be dosed within 30 min (no longer than 1 hour) after a meal.
• Drug Taletrectinib,Famotidine
  A single oral dose of 20 mg famotidine. On the morning of Day 2 of Part 2 Treatment C, taletrectinib 400 mg should be administered within 30 min and no longer than 1 hour after a meal, 10 hours after the famotidine dose from the prior evening; a final oral dose of 20 mg famotidine will be administrated 2 hours later.

Primary outcome measures

• Cmax of Taletrectinib [Time frame: Pre-dose to 264 hours post dose on Day 1, Day 15 and Day 30]
• AUClast of Taletrectinib [Time frame: Pre-dose to 264 hours post dose on Day 1, Day 15 and Day 30]
• AUCinf of Taletrectinib [Time frame: Pre-dose to 264 hours post dose on Day 1, Day 15 and Day 30]

Secondary outcome measures (12)

• Tmax of Taletrectinib [Time frame: Pre-dose to 264 hours post dose on Day 1, Day 15 and Day 30]
• λz of Taletrectinib [Time frame: Pre-dose to 264 hours post dose on Day 1, Day 15 and Day 30]
• t½ of Taletrectinib [Time frame: Pre-dose to 264 hours post dose on Day 1, Day 15 and Day 30]
• CL/F of Taletrectinib [Time frame: Pre-dose to 264 hours post dose on Day 1, Day 15 and Day 30]
• Vz/F of Taletrectinib [Time frame: Pre-dose to 264 hours post dose on Day 1, Day 15 and Day 30]
• AUCextr% of Taletrectinib [Time frame: Pre-dose to 264 hours post dose on Day 1, Day 15 and Day 30]
• Physical Examinations including assessment of general appearance, skin, head and neck, chest, abdomen, spine and limbs, neurologic system [Time frame: About 2 months]
• Severity of adverse events (AEs) and the number of participants with treatment-emergent adverse event (TEAE) [Time frame: About 2 months]
• Vital signs: Systolic blood pressure(mmHg) [Time frame: About 2 months]
• Vital signs: Diastolic blood pressure(mmHg) [Time frame: About 2 months]
• Vital signs: Heart rate (beats/min) [Time frame: About 2 months]
• Vital signs: Respiratory rate (breaths/min) [Time frame: About 2 months]

Eligibility criteria

Inclusion criteria

• The participant must voluntarily sign an Informed Consent Form (ICF) prior to any study-related procedures.
• Participants are able to communicate well with Investigators and complete the study in accordance with the protocol.
• Between the ages of 18 and 55 years (inclusive) at the time of signing the ICF.
• Healthy adult participants (healthy refers to the status of no clinically relevant abnormalities identified through medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory examinations).
• Body weight is greater than 50.0 kg at Screening and the body mass index (BMI) is between 19 and 26 kg/m2.
• Males and/or females who meet any of the following criteria:

• For males (irrespective of surgical sterilization \[vasectomy\]): agree to use effective contraception methods during the study intervention period and for at least 90 days after the last dose of study drug or agree with complete abstinence; and agree not to donate sperm during this same time period.
• Females without menses for at least 1 year prior to Screening or documented to be surgically sterilized. Females of childbearing potential (FOCBP) must agree to use 2 concurrent highly effective methods of contraception or agree with complete abstinence from sexual intercourse from signing of the ICF until 45 days after the last dose of study drug. Usage of hormonotherapy for contraception should be recorded as well.
• For all females of childbearing potential, a negative pregnancy test must be obtained within 1 day before the first dose of study drug. Female participants of non-childbearing potential must meet at least 1 of the following criteria:

• Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state.
• Have undergone a documented hysterectomy and/or bilateral oophorectomy.
• Have medically confirmed ovarian failure. All other female participants (including female participants with tubal ligations) are considered to be of childbearing potential.
• Must agree to avoid strenuous exercise from 72 hours prior to dosing on Day 1 of Period 1 until the EOT/ET visit.
• Able to sign the informed consent and to comply with the protocol.
• Patients with adequate organ function meeting the following criteria:

• Serum total bilirubin: ≤1×ULN.
• Estimated creatinine clearance (CLcr) ≥90 mL/min as calculated using the methodstandard for the institution (e.g., Cockcroft-Gault Equation).

Exclusion criteria

• Evidence or history of clinically significant hematology, kidney, endocrine, lung, gastrointestinal, cardiovascular, liver, mental, neurological, or allergic diseases (including drug allergies, but not including untreated, asymptomatic seasonal allergies at the time of dosing).
• According to the Investigator's judgment, there are clinically significant abnormal laboratory results (hematology, serum chemistry, coagulation, and urinalysis).
• Any active or unstable medical condition as judged by the Investigator.
• The Investigator believes that the participant may be at increased risk of eye disease or have a history of eye disease, such as glaucoma, retinal shedding, glass turbidity, moth disease,etc.
• Impaired cardiac function including clinically significant arrhythmias or clinically significant abnormality including but not limited to any of the following at Screening and Admission,repeat testing is allowed for verification, at the discretion of the Investigator:

• Heart rate <50 beats per minute (bpm) or >100 bpm (taken during supine blood pressure measurement).
• Systolic blood pressure <90 mmHg or ≥140 mmHg; diastolic blood pressure <50 mmHg or ≥90 mmHg (supine blood pressure measurement).
• The 12-lead ECG shows that the QTc is >450 milliseconds (msec) or the QRS duration exceeds >120 msec. If the QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc and QRS values should be used to determine the participant's eligibility.
• History of febrile illness within 5 days prior to the first dose of study drug.
• Positive blood screen for human Hepatitis B virus surface antigen, hepati is C virus antibody (HCV Ab), or human immunodeficiency virus (HIV) antibody.
• Pregnancy or lactation/breastfeeding.
• Use of food or drugs that are known to be strong or moderate cytochrome P450 (CYP)3A4/5 inhibitors or inducers or to be P-glycoprotein inhibitors within 14 days prior to the first dose of study drug until the EOT/ET visit.
• Consumption of Seville oranges or grapefruit-containing foods or beverages within 14 days prior to the first dose of study until the EOT/ET visit.
• Participants who have used prescription or over-the-counter (OTC) medication (other than ≤2 g/day acetaminophen or ≤800 mg/day ibuprofen or allowed contraception methods), vitamins, or herbal remedies, within 2 weeks or 5 half-lives before study drug administration, whichever is longer.
• Participants who have received live vaccines or attenuated vaccines within 28 days prior to the first dose of study drug until the EOT/ET visit.
• Participants who have received any investigational drug, device, biologic, or other agent (within 60 days or 5 half-lives, whichever is longer) prior to study drug administration on Day 1.
• Participants who are reluctant to stop consuming caffeinated or purine-containing foods (e.g., coffee, tea, cola, chocolate) from 72 hours prior to the first dose of study drug until the EOT/ET visit.
• History of regular alcohol consumption exceeding 14 drinks/week (1 drink =12 ounces \[360 mL\] beer, or 5 ounces \[150 mL\] of wine, or 1.5 ounces \[45 mL\] of hard liquor), or participants who are unwilling to stop drinking alcohol from 72 hours prior to the first dose of study drug until the EOT/ET visit.
• Use of tobacco- or nicotine-containing products ≥5 cigarettes per day, or participants who are unwilling/unable to stop tobacco- or nicotine-containing products from 72 hours prior to the first dose of study drug to the EOT/ET visit.
• A positive urine drug screen.
• A positive blood or breath test for alcohol.
• Underwent major surgery within 6 months prior to the first dose of study drug.
• Blood donation or blood loss within 3 months prior to the first dose of study drug of ≥400 mL.
• Plasma donation within 30 days prior to the first dose of study drug.
• Participants with gastrointestinal, liver, kidney disease, or other diseases known to interfere with drug absorption, distribution, metabolism, or excretion within 3 months prior to screening and during the Screening Period, or have a medical history of platelet reduction induced by heparin or heparin-induced thrombocytopenia.
• Unwilling or unable to comply with the dietary or other guidelines described in this protocol.
• Participants who are investigational site staff members directly involved in the conduct of the study or are their family members; site staff members otherwise supervised by the Investigator, or participants who are Nuvation Bio employees directly involved in the conduct of the study.
• Venous access considered inadequate for PK sample collection; history or evidence of adverse symptoms associated with phlebotomy or blood donation.
• The Investigator judges that the participant is not suitable to participate in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07742384 · NUV-106-C122

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗