SafetyPhase 1NCT07878481
A First-in-Human SAD and MAD Study in HV to Evaluate Oral YR011 Tablet
A Phase 1 study testing Kv1.3 potassium channel blocker (PA032, investigational oral small-molecule drug) in people with Safety and Tolerability, run by Hangzhou Yirui Pharmaceutical Technology Co., Ltd.
Trial summary
This is a Phase I clinical trial (protocol number: YR-011-B07) sponsored by Hangzhou Yirui Pharmaceutical Technology Co., Ltd., focusing on the novel oral small-molecule drug YR011 (active ingredient: PA032, a Kv1.3 channel blocker). Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Safety, Tolerability, Pharmacokinetic
- What is being tested?
- Kv1.3 potassium channel blocker (PA032, investigational oral small-molecule drug)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2027to 31 Dec 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants who meet all the following criteria could be enrolled in this study:
- Written informed consent obtained from the participant in compliance with all local legal requirements.
- Male or female participant aged between 18 and 60 years (extremes included).
- Body mass index (BMI) between 18-32 kg/m2 (extremes included) and body weight less than 120 kg.
- Males must use a condom or remain abstinent during the trial and for 3 months after their last dose of study medication. And a fertile man's female partner must not try to become pregnant during the study.
- Female participants of childbearing potential must be established on a highly effective method of contraception (The recommended birth control methods are: Implantable (e.g. Implanon(r)), injectable (e.g. Depo-Provera(r)), insertable (e.g. NuvaRing®), Mirena (r) (LNG-IUS)), Combined oral contraceptives pill or progestin-only pill, Evra patch®, Intrauterine device (e.g. ParaGard(r), copper T) or Female sterilization, Male sterilization. The recommended birth control methods must be taken at least 3 weeks prior to screening (i.e., to ensure the contraceptive method has taken effect).) prior to dosing and until 3 months after their last dose in combination with male partner's use of a condom during the trial and for 3 months after the last dose.
- Free from any clinically relevant illness or disease that may adversely affect the safety of the participant, or the integrity of the study as determined by medical history, physical examination, safety laboratory, and other assessments.
- Participants must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Without other intestinal diseases such as irritable bowel syndrome and acute diarrhea due to any infection.
Who cannot join
- If the participants meet any of the following criteria, they cannot be enrolled in this
- Pregnant or breastfeeding women.
- Participants with difficulty swallowing.
- Severe infections requiring parenteral antibiotic therapy within 4 weeks before screening, such as sepsis or severe pneumonia.
- Any clinically relevant conditions, such as cerebral stroke, myocardial infarction, heart failure, unstable angina pectoris, and severe cardiac arrhythmia within 6 months before screening.
- Gastrointestinal, hepatic, or renal diseases or any other abnormalities known to interfere with drug absorption, distribution, metabolism, or excretion (within 6 months).
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- Supine blood pressure with systolic blood pressure outside the range of 90-140 mmHg and diastolic blood pressure outside the range of 40-90 mmHg, confirmed by repeat measurement at screening or baseline (Day -1) based on the Investigator's judgment.
- Existing renal impairment (e.g., estimated glomerular filtration rate eGFR <60 mL/min).
- Presence of hepatic impairment: Child-Pugh A, B, or C and/or transaminase levels exceeding the upper limit of normal (i.e., serum total bilirubin >= 1.5 x upper limit of normal [ULN], ALT or AST levels > ULN).
- Diabetes mellitus, regardless of control status at screening.
- Hyperthyroidism or hypothyroidism.
- Malignancy within 5 years, except for basal cell carcinoma of the skin, squamous cell carcinoma, or cured carcinoma in situ of the cervix.
- Any major surgery within 6 months before screening.
- Positive test results at screening for HBV (HBsAg positive), HCV (anti-HCV positive), or human immunodeficiency virus types I and II (anti-HIV I/II positive), or Treponema pallidum antibody (anti-TP positive).
- Individuals with congenital or acquired immune system deficiency.
- Resting heart rate outside the range of 40-100 bpm, confirmed by repeat measurement at screening or baseline (Day -1) based on the Investigator's judgment.
- Participants with abnormal ECG at screening or baseline (Day -1). The inclusion of any participant with ECG abnormalities in the study must be approved by the Principal Investigator or a medically qualified Sub-Investigator with a signed record.
- QT interval by Fridericia's correction method (QTcF) >450 ms (male) or >470 ms (female), or PR outside the range of 120-220 ms, confirmed by one repeat test at screening or baseline (Day -1) visit; or a history of risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome); or use of concomitant medications that prolong the QT/QTc interval.
- History of severe psychiatric illness or currently receiving treatment for psychiatric illness; participants with prior epileptic seizures or convulsions (lifetime, except febrile convulsions), including absence seizures.
- Use of any concomitant medication (including prescription drugs, over-the-counter drugs [e.g., aspirin, acetaminophen, ibuprofen], herbal medicines [including traditional Chinese medicine products], dietary supplements and cough syrups, prescription or over-the-counter antacids, etc.) within 14 days before study drug administration (or within 5 half-lives of the concomitant medication, whichever is longer).
- Current use of strong inhibitors/inducers/substrates of CYP3A4, CYP3A5, and CYP2C8 with a narrow therapeutic index within 14 days before study drug administration.
- Receipt of another investigational drug, biologic, or device therapy within 1 month after screening or within 5 half-lives of the study drug (whichever is longer).
- Allergy to PA032 (active substance) or any excipient.
- History of drug abuse, illicit drug use, or alcohol abuse within 1 year before screening (more than 14 units/week, 1 unit = 285 mL beer, or 250 mL spirits, or 125 mL wine) or unwillingness to abstain from alcohol and drugs (medications) throughout the entire study.
- Regular use of nicotine-containing products (including but not limited to cigarettes, electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patches, or nicotine gum) or positive urine cotinine test at baseline (Day -1). Occasional users of nicotine-containing products may participate but must avoid use during the screening period and throughout the study.
- Positive urine drug test at screening.
- Positive alcohol breath test at admission (Day -1).
- Central nervous system, cardiovascular, pulmonary, hepatic, hematopoietic system diseases, renal, metabolic, gastrointestinal, urinary, immune, endocrine diseases, severe allergies, systemic allergic rash (including urticaria), psychiatric illness, evidence of abnormal liver function tests, evidence of abnormal renal function tests, or other abnormalities that may affect the participant's ability to participate or may confound the study results.
- Poor peripheral venous access (defined as more than 3 failed puncture attempts).
- Blood or plasma donation within 60 days before dosing. Participants who received blood product infusion within 90 days before screening.
- Male participants planning to donate sperm or female participants planning to donate eggs (oocytes) during the study and within 3 months after the last dose.
- Employees of the contract research organization, trial site, or sponsor, or immediate family members of employees.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A First-in-Human, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of Oral YR011 Tablets in Healthy Participants
This is a Phase I clinical trial (protocol number: YR-011-B07) sponsored by Hangzhou Yirui Pharmaceutical Technology Co., Ltd., focusing on the novel oral small-molecule drug YR011 (active ingredient: PA032, a Kv1.3 channel blocker). The trial aims to evaluate the safety, tolerability, and pharmacokinetics (PK) of YR011 in healthy adult participants.
The trial has two stages: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD), with about 64 participants total (32 per stage). Participants are divided into 4 cohorts per stage (8 people per cohort), randomized 6:2 to receive YR011 or placebo in a double-blind manner. For the SAD stage, 4 dose levels are tested as a single oral dose under fasting conditions; for the MAD stage, 4 dose levels are given twice daily for 7 days plus one extra dose on Day 8.
Read more
Key procedures include screening (up to 28 days before enrollment), baseline assessments, drug administration, and follow-up (7 days for SAD, 14 days for MAD). Safety is the primary endpoint (measured by treatment-related adverse events), with secondary endpoints including PK parameters (e.g., plasma concentration, half-life) and dose accumulation. Eligible participants are 18-60 years old, healthy, and able to comply with trial procedures; those with major diseases, drug allergies, or recent medication use are excluded.
The trial follows ICH-GCP and FDA regulations, with a Safety Review Committee overseeing dose escalation and safety monitoring. All data is collected via electronic case report forms (eCRFs) and kept confidential.
Read the detailed description
This is a randomized, double-blind, placebo-controlled Phase Ⅰ study. The purpose is to investigate the safety, tolerability, pharmacokinetics (PK) of YR011 in adult healthy participants following oral single and multiple ascending dose administration and the recommended dose to be used in the phase Ⅱ study.
This study consists of 2 stages:
Stage 1 (SAD):
The plan is to enroll approximately 32 eligible healthy participants in 4 cohorts. At least 4 cohorts will be studied, with approximately 8 participants in each cohort. Participants will be randomized at a 6:2 ratio to receive YR011 or placebo in a double-blind fashion, i.e. for 8 participants in a cohort, 6 participants will be randomized to receive active drug and 2 participants randomized to receive placebo. Sentinel dosing (1 participant to receive YR011 and 1 participant to receive placebo) will be used in each cohort to ensure adequate safety and tolerability evaluation before administering YR011 or placebo to the remainder of the participants within the cohort. After blinded review by the Safety Review Committee (SRC) of 24-hour post-dose safety and tolerability data from the sentinel group, the remaining 6 participants of each cohort may be dosed, provided that the adverse event (AE) profile in the sentinel participants is considered acceptable.
Four dose levels are planned. However, an additional cohort with a designated dose may be further studied if safety is confirmed in the previous cohorts, as decided by the SRC. The next dose level can only be studied after the SRC reviews the safety data of the previous dose level. For each participant, the drug will be administered once under fasting condition.
Pharmacokinetic blood samples will be collected up to 48 hours after dosing. Participants will be admitted to the Clinical Unit on Day -1, remain at the Clinical Unit until 48 hours post-dose on Day 3 (3 overnight stays), and will return 7 days after dosing for a Follow-up Visit.
The adjustment of the ascending dose will be based on the following rules:
Dose escalation will start from the lowest dose and proceed in the planned escalating sequence. After all participants have received the previous dose of the drug, the investigator and the sponsor will decide whether to escalate to the next dose level. In each dose group of participants, if 1/2 or more participants experience grade 2 or above adverse events (AEs, regardless of the AEs' relation to the study drug), or 1/3 or more participants experience grade 3 or above AEs (regardless of the AEs' relation to the study drug), or one or more participants experience serious adverse events (SAEs, regardless of the AEs' relation to the study drug), dose escalation will be terminated.
After the Stage 1 (SAD) is completed, the sponsor will decide whether to proceed with Stage 2 (MAD), suspend the study for an interim analysis, or terminate the study.
Stage 2(MAD):
There will be approximately 32 eligible healthy participants enrolled in 4 cohorts. Each cohort will include 8 participants. Participants will be randomized at a 6:2 ratio to receive YR011 or placebo in a double-blind fashion, i.e., for 8 participants in a cohort, 6 participants will be randomized to receive active drug and 2 participants randomized to receive placebo. Unlike the single-dose regimen, sentinel dosing within cohorts is not required in the multiple-dose regimen.
Four dose levels as decided by SRC are planned, and will be orally administered twice daily for 7 days, and 1 more dose on the 8th day, followed by a 7-day post-dose follow-up period under fasting condition. However, the dosage and administration method may be modified based on the findings in stage 1 and any new findings in stage 2. Pharmacokinetic blood samples will be collected up to 48 hours after dosing. Participants will be admitted to the Clinical Unit on Day -1, remain at the Clinical Unit until D10 (10 overnight stays), and will return 7 days after dosing for a Follow-up Visit.
The adjustment of the ascending dose will be based on the following rules:
Dose escalation will start from the lowest dose and proceed in the planned escalating sequence. After all participants have received the previous dose of the drug, the investigator and the sponsor will decide whether to escalate to the next dose level. In each dose group of participants, if 1/2 or more participants experience grade 2 or above adverse events (AEs, regardless of the AEs' relation to the study drug), or 1/3 or more participants experience grade 3 or above AEs (regardless of the AEs' relation to the study drug), or one or more participants experience serious adverse events (SAEs, regardless of the AEs' relation to the study drug), dose escalation will be terminated. Safety Review Committee (SRC) The SRC will be comprised of Independent, subject-matter-expert individuals (as qualified by education, training and experience to perform their respective task), not directly involved in the study conduct, for an unbiased review of the trial's emerging safety data and to help inform dose escalation decisions.
A pharmacokinetics expert and other participant matter experts may participate as needed. The SRC will be responsible for ongoing review of safety, tolerability, and clinical laboratory results, and available PK data, and deciding:
- To escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or higher) in single-dose cohorts (based on a review of available data, including at least 48 hours post-dose safety data and clinical laboratory results from each of the participants in the current cohort); 2) To escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or higher) in multiple-dose cohorts (based on a review of available data, including at least 48 hours post last dose safety data from each of the participants in the current cohort); 3) To add additional dose cohort(s) in either the single- or multiple-dose studies.
- To decide whether sentinel participants are needed in MAD cohorts. In addition, if ≥ 2 subjects on drug develop the same or similar AE of moderate intensity or if 1 subject develops a severe or serious AE that is considered possibly or probably related to study drug administration, further dosing will be withheld until the SRC investigates the events. Based on this assessment, the SRC will determine if the study should be terminated or continued and whether modification of planned dose levels and/or implementation of additional safety monitoring is indicated.
- Conditions
- Safety, Tolerability, Pharmacokinetic
- Being tested
- Kv1.3 potassium channel blocker (PA032, investigational oral small-molecule drug), Placebo
- Keywords
- YIRUI pharma, KV1.3, Health volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Kv1.3 potassium channel blocker (PA032, investigational oral small-molecule drug)Drug
Highly selective Kv1.3 potassium channel blocker (active ingredient: PA032) - oral tablet formulation, administered as single ascending doses or multiple ascending doses (twice daily for 7 days + 1 extra dose on Day 8) under fasting conditions.
PlaceboDrug
The placebo intervention in this study is a matched oral tablet formulationcontaining inactive ingredients (e.g., excipients like microcrystalline cellulose, lactose) with no pharmacological activity
| Study group | Role | What they receive |
|---|---|---|
| YR011 | Active comparator | Active arm: Participants receive the investigational drug YR011 at a specific dose. Receives: Drug: Kv1.3 potassium channel blocker (PA032, investigational oral small-molecule drug) |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of treatment- Emergent adverse events (TEAE)
safety assessment will be based on the incidence of treatment- Emergent adverse events (TEAE) through out the treatment period and until the post-treatment follow-up period
Measured: From date of randomization until the last date of the post-treatment follow-up period, up to 44 days after informed consent.
Secondary outcomes (5)
Plasma concentration of YR011
blood samples will be taken at various timepoints before and after single and multiple dosing of the study drug
Measured: During treatment period from the first dose to the last dose (up to Maximum of 10 days)
Peak Plasma Concentration of YR011
blood samples will be taken at various timepoints before and after single and multiple dosing of the study drug to assess the Cmax of YR011
Measured: During treatment period from the first dose to the last dose (up to Maximum of 10 days)
Time to peak plasma concentration of YR011
blood samples will be taken at various timepoints before and after single and multiple dosing of the study drug to assess the Tmax of YR011
Measured: During treatment period from the first dose to the last dose (up to Maximum of 10 days)
Area under the plasma concentration versus time curve (AUC) of YR011
blood samples will be taken at various timepoints before and after single and multiple dosing of the study drug to assess the AUC of YR011
Measured: During treatment period from the first dose to the last dose (up to Maximum of 10 days)
Half life of YR011 (T1/2)
blood samples will be taken at various timepoints before and after single and multiple dosing of the study drug to assess the T1/2 of YR011
Measured: During treatment period from the first dose to the last dose (up to Maximum of 10 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2026
- Study start1 Jan 2027 (estimated)
- Primary completion30 Oct 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SafetyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hangzhou Yirui Pharmaceutical Technology Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07878481
- Sponsor's protocol ID
- YR011-B07
- Status last verified
- Oct 2026
- First submitted
- 9 Oct 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No