A Phase I Study of LuoXin Innovate (LXI-15028) in Healthy Chinese Subjects to Evaluate the Pharmacokinetics, Safety and Tolerability.

NCT03458650 | Completed Phase 1

• 1 other identifier: NE821605
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

"This study is a single-center, randomized, double-blinded and placebo-controlled trial designed not only to assess pharmacokinetics, safety and tolerability of LXI-15028 but also to evaluate the pharmacokinetic characteristics of main metabolite M1 in vivo in 38 healthy adult Chinese subjects after receiving escalating single oral doses of 50 mg, 100 mg and 200 mg and multiple oral doses of 100 mg of LXI-15028.

Conditions

Healthy

Outcome Measures

Primary Outcomes (34)

• Pharmacokinetic parameter： Cmax

  The maximum plasma concentration (Cmax) after single dose LXI-15028

  72 h after receiving single oral dose

• Pharmacokinetic parameter： Tmax

  The peak time (Tmax) after single dose LXI-15028

  72 h after receiving single oral dose

• Pharmacokinetic parameter： T1/2

  The elimination half-life T1/2 after single dose LXI-15028

  72 h after receiving single oral dose

• Pharmacokinetic parameter： Kel

  The eliminate rate constant after single dose LXI-15028

  72 h after receiving single oral dose

• Pharmacokinetic parameter：Mean Residence Time(MRT)

  The mean residence time after single dose LXI-15028

  72 h after receiving single oral dose

• Pharmacokinetic parameter: Area Under plasma Concentration(AUC 0-24h)

  The area under plasma concentration -time curve from 0 time ot 24 h after single dose LXI-15028

  24h after receiving single oral dose

• Pharmacokinetic parameter: AUC 0-last

  The area under plasma concentration- time curve from 0 time to sampling time of the last measurable concentration after single dose LXI-15028

  72h after receiving single oral dose

• Pharmacokinetic parameter: AUC 0-inf

  The area under plasma concentration-time curve from adminstration (0)to infinity after single dose LXI-15028

  72h after receiving single oral dose

• Pharmacokinetic parameter: Vd/F

  The apparent volume of distribution after single dose LXI-15028

  72h after receiving single oral dose

• Pharmacokinetic parameter: Css min

  The trough concentration at steady state(Css min) after multiple doses

  predose at day 8, 9, and 10, 72 h after receiving last multiple oral doses

• Pharmacokinetic parameter: Css max

  The peak concentration at steady state (Css max) after multiple doses

  72 h after receiving last multiple oral doses

• Pharmacokinetic parameter: Css av

  The average concentration at steady state (Css, av)after multiple doses

  72 h after receiving last multiple oral doses

• Pharmacokinetic parameter: Tss max

  The peak time after multiple doses

  72 h after receiving last multiple oral doses

• Pharmacokinetic parameter: Tss,1/2

  The steady-state clearance half-time after multiple doses

  72 h after receiving last multiple oral doses

• Pharmacokinetic parameter: CLss/F

  Total body clearance after multiple doses

  72 h after receiving last multiple oral doses

• Pharmacokinetic parameter: coefficient of fluctuation (DF)

  coefficient of fluctuation after multiple doses

  72 h after receiving last multiple oral doses

• Pharmacokinetic parameter: Area Under plasma Concentration at steady state (AUC ss)

  The area under plasma concentration-time curve at steady state after multiple doses

  72 h after receiving last multiple oral doses

• Pharmacokinetic parameter: Rac

  The accumulation coefficient after multiple doses

  72 h after receiving last multiple oral doses

• Physical examination value of single dose

  This measure is a composite. Evaluate safety and tolerability of single dose in Physical examination that should cover the head, eyes, ears, nose, throat, cardiovascular system, skin, musculoskeletal, respiratory system, digestive system, urinary system and nervous system and changes of each item from the baseline are summarized. The measurement results of each subject are summarized by different severity. All physical examination results during this trial will be listed in details.

  Baseline to Day 4 after receiving single oral dose

• Vital signs value of single dose

  The measure is a composite.Evaluate safety and tolerability of single dose in Vital signs value that including blood pressure (Systolic blood pressure/Diastolic blood pressure), pulse, body temperature，each vital sign examination values at each evaluation time point and their changes relative to the baseline will be summarized. All vital sign results should be listed. The listed vital signs are compared with normal ranges to determine whether is abnormal. The examination results that are divided into higher than normal range, normal and lower than normal range will be summarized by number of cases (n) and percentage (%). The results of abnormalities(\> or \< normal range) are listed.

  Up to 3weeks

• 12-lead ECG value of single dose

  Evaluate safety and tolerability of single dose in 12-lead ECG value that including ventricular rate (beats/min), PR interval (ms), QRS (ms) , QT(ms),QTc (ms)， the examination results of each ECG parameters and their changes from baseline will be summarized at each time point. Meanwhile, all 12-lead ECG examination results will be listed in details.

  Up to 3 weeks

• Blood routine value of single dose

  Evaluate safety and tolerability of single dose in blood routine value that including White blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), hematocrit (Hct), platelet, neutrophils, lymphocytes, monocytes, eosinophils, basophils, absolute neutrophil counts (ANC);and list all the result.

  Baseline to Day 4 after receiving single oral dose

• Urine routine value of single dose

  Evaluate safety and tolerability of single dose in urine routine value that including specific gravity, pH, proteins, ketone,occult blood; and list all the result.

  Baseline to Day 4 after receiving single oral dose

• Blood coagulation value of single dose

  Evaluate safety and tolerability of single dose in blood coagulation value that including International normalized ratio (INR), activated partial thromboplastin time (aPTT), prothrombin time (PT); and list all the result.

  Baseline to Day 4 after receiving single oral dose

• Blood biochemistry value of single dose

  Evaluate safety and tolerability of single dose in blood biochemistry value that including Cholesterol, total proteins, albumin, total bilirubin, Conjugated bilirubin, creatinine, creatine kinase (CPK), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyltransferase (γ-GT), magnesium, sodium, potassium, chlorine, total calcium, inorganic phosphorus, lactate dehydrogenase (LDH), glucose, uric acid, triglyceride (TG); and list all the result.

  Baseline to Day 4 after receiving single oral dose

• Adverse events of single dose

  The adverse events are encoded using MedDRA 20.1. According to system organ classification (SOC) and preferred term (PT), all TEAE, investigational drug-related TEAE, Serious Adverse Event, investigational drug-related SAE, and TEAE causing premature withdrawal from this study will be separately summarized by different dose groups, including number of subjects experiencing Adverse Event, percentage and number of AE cases. The summary results are sorted according to the ranking number of cases of all subjects experiencing AE. All AE and SAE are listed by different dose groups.

  Up to 3 weeks

• Physical examination value of multiple doses

  The measure is a composite. Evaluate safety and tolerability of multiple doses in Physical examination that should cover the head, eyes, ears, nose, throat, cardiovascular system, skin, musculoskeletal, respiratory system, digestive system, urinary system and nervous system and changes of each item from the baseline are summarized. The measurement results of each subject are summarized by different severity. All physical examination results during this trial will be listed in details.

  Baseline to Day 21 after receiving the first dose

• Vital signs value of multiple doses

  The measure is a composite.Evaluate safety and tolerability of multiple doses in Vital signs value that including blood pressure(Systolic blood pressure/Diastolic blood pressure), pulse, body temperature.Each vital sign examination values at each evaluation time point and their changes relative to the baseline will be summarized. All vital sign results should be listed. The listed vital signs are compared with normal ranges to determine whether is abnormal. The examination results that are divided into higher than normal range, normal and lower than normal range will be summarized by number of cases (n) and percentage (%). The results of abnormalities(\> or \< normal range) are listed.

  Baseline to Day 21 after receiving the first dose

• 12-lead ECG value of multiple doses

  Evaluate safety and tolerability of multiple doses in 12-lead ECG value that including ventricular rate (beats/min) ，PR interval (ms)， QRS (ms) ,，QT(ms)， QT interval (QTc )(ms). The examination results of each ECG parameters and their changes from baseline will be summarized at each time point. Meanwhile, all 12-lead ECG examination results will be listed in details.

  :Baseline to Day 21 after receiving the first dose

• Blood routine value of multiple doses

  Evaluate safety and tolerability of multiple doses in blood routine value that including White blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), hematocrit (Hct), platelet, neutrophils, lymphocytes, monocytes, eosinophils, basophils, absolute neutrophil counts (ANC); and list all the result.

  Baseline to Day 21 after receiving the first dose

• Urine routine value of multiple doses

  Evaluate safety and tolerability of multiple doses in urine routine value that including specific gravity, potential of hydrogen (pH), proteins, ketone,occult blood; and list all the result.

  Baseline to Day 21 after receiving the first dose

• Blood coagulation value of multiple doses

  Evaluate safety and tolerability of multiple doses in blood coagulation value that including International normalized ratio (INR), activated partial thromboplastin time (aPTT), prothrombin time (PT);

  Baseline to Day 21 after receiving the first dose

• Blood biochemistry value of multiple doses

  Evaluate safety and tolerability of multiple doses in blood biochemistry value that including Cholesterol, total proteins, albumin, total bilirubin, Conjugated bilirubin, creatinine, creatine kinase (CPK), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyltransferase (γ-GT), magnesium, sodium, potassium, chlorine, total calcium, inorganic phosphorus, lactate dehydrogenase (LDH), glucose, uric acid, triglyceride (TG); and list all the result.

  Baseline to Day 21 after receiving the first dose

• Adverse events of multiple doses

  The adverse events are encoded using MedDRA 20.1. According to system organ classification (SOC) and preferred term (PT), all treatment-emergent adverse event (TEAE), investigational drug-related TEAE, serious adverse event (SAE), investigational drug-related SAE, and TEAE causing premature withdrawal from this study will be separately summarized by different dose groups, including number of subjects experiencing AE, percentage and number of adverse event (AE) cases. The summary results are sorted according to the ranking number of cases of all subjects experiencing AE. All AE and SAE are listed by different dose groups.

  Up to 6 weeks

Secondary Outcomes (20)

• Pharmacokinetic parameter of major metabolite(M1): Cmax

  72 h after receiving single oral doses

• Pharmacokinetic parameter of major metabolite(M1): Tmax

  72 h after receiving single oral doses

• Pharmacokinetic parameter of major metabolite(M1): T1/2

  72 h after receiving single oral doses

• Pharmacokinetic parameter of major metabolite(M1): Kel

  72 h after receiving single oral dose

• Pharmacokinetic parameter of major metabolite(M1): MRT

  72 h after receiving single oral dose

Study Arms (3)

LXI-15028 50 mg

EXPERIMENTAL

For 50 mg dose groups, each is planned to enroll 12 healthy subjects (investigational drug :placebo=10:2), half males and half females. Five subjects of each gender will receive LXI-15028, while 1 subject of each gender will receive placebo

Drug: LXI-15028 50mg; Drug: Placebo

LXI-15028 100 mg

EXPERIMENTAL

100 mg dose group plans to enroll 14 healthy subjects (investigational drug:placebo=10:4), half males and half females. Five subjects of each gender will receive LXI-15028, while 2 subjects of each gender will receive placebo. Intra-group randomization will be implemented in each dose group; each subject will receive either LXI-15028 or placebo.

Drug: LXI-15028 100mg; Drug: Placebo

LXI-15028 200 mg

EXPERIMENTAL

200 mg dose groups, each is planned to enroll 12 healthy subjects (investigational drug :placebo=10:2), half males and half females. Five subjects of each gender will receive LXI-15028, while 1 subject of each gender will receive placebo

Drug: LXI-15028 200mg; Drug: Placebo

Interventions

LXI-15028 50mg DRUG

In escalated single-dose study, the subjects in each dose group will receive single oral dose of 50 mg LXI-15028 tablet or 1 matching placebo tablet at fasted state,

LXI-15028 50 mg

LXI-15028 100mg DRUG

100 mg LXI-15028 tablet or matching placebo 1 tablet at fasted state, In multiple-dose study, the subjects who administered 100mg single dose will continuously receive oral 100 mg LXI-15028 tablet or 1 matching placebo tablet once daily (QD) for 10 times.

LXI-15028 100 mg

LXI-15028 200mg DRUG

single oral dose 2 100 mg LXI-15028 tablets or 2 matching placebo tablets at fasted state

LXI-15028 200 mg

Placebo DRUG

matching placebo tablets

LXI-15028 100 mg; LXI-15028 200 mg; LXI-15028 50 mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subjects should voluntarily participate in this trial and sign the informed consent form prior to conducting any trial-related procedures;
• Gender: male or female healthy subjects; Age: 18\~45 years old (including 18 and 45 years old);
• The body weight should be equal or greater than 50.0 kg for male and 45.0 kg for female. Body weight index (BMI)= body weight (kg)/\[height(m)×height(m)\], should be within the range from 19 to 25 (including 19 and 25);
• In the past three years, no history or presence of cardiovascular, hepatic, renal, respiratory, hematological and lymphatic, endocrine, immunological, mental, neurological and gastrointestinal disease; no history of surgery;
• The subjects (including males and females) agree to use medically approved contraceptive methods during the trial period and within 3 months after the end of the trial in order to avoid pregnancy; medically approved contraceptive methods include intrauterine device, physical barrier (male condom, female condom), subcutaneous implant, sustained-release contraceptive, bilateral salpingectomy, bilateral tubal ligation, bilateral vas ligation, etc.;
• The subjects agree not to donate sperms (males) or ova (females) at least 7 days before the first dose, during the study and within 3 months after ending of this study.

You may not qualify if:

• The subjects with allergic constitution, for example those with bronchial asthma, allergic to food or pollen, allergic to two or more drugs or those with known history of allergy ; or the subjects with any serious adverse response to Proton Pump Inhibitor or P-CABs previously (e.g., omeprazole, rabeprazole, lansoprazole and TAK-481 ), or known allergy to penicillins or cephalosporins;
• The investigator determines that it may potentially affect absorption, distribution, metabolism or elimination of investigational drug (e.g. organ dysfunction);
• The subjects with a history of drug abuse or drug abuse screening positive;
• The subjects received any drugs (including prescription drugs, Over-The-Counter drugs, herbal medicines, etc.) within 1 month before the screening or are taking drugs, especially CYP3A inhibitor or inducer (see Appendix 1);
• The subjects with clinical significant physical examination abnormalities determined by investigator;
• Heart rate\<50 beats/min or \>100 beats/min or QTc interval prolonged (male QTcF≥430ms, female QTcF≥450ms) or QRS≥120 msec or other clinically significant ECG abnormalities; 7) The subjects with sitting blood pressure: systolic pressure \<90mmHg or ≥ 140mmHg, diastolic pressure ≥90mmHg or \<60mmHg, which shows clinical significant abnormalities determined by investigators
• The subjects with any biomarker value of Aspartate aminotransferase (AST),Alanine aminotransferase(ALT), Alkaline phosphatase(ALP),r-Glutamyl Transferase (r-GT), total bilirubin, creatinine above the upper limit of normal or with other clinical significant laboratory examination abnormalities judged by investigators
• The subjects with presence of one of the following infectious diseases;
• Virological determination indicates hepatitis B virus surface antigen (HBsAg) positive or anti-hepatitis C virus antibody positive;
• Acquired human immunodeficiency virus determination indicates infection; (anti-human immunodeficiency virus antibody positive)
• Treponema pallidum infection (anti-treponema pallidum-specific antibody positive).
• Currently smoking or quitting smoking less than 3 months before screening or tobacco screening positive;
• Chronical alcohol user within 5 years prior to screening, or alcohol consumption of more than 14 unit alcohol per week (1 unit alcohol equal to 360 mL beer, or 150 mL grape wine, or 45 mL wine of 40 degree) within 6 months prior to screening;
• Alcohol screening test positive or alcohol intake within 72 h prior to screening;
• Daily drinking a large amount (above 1000 mL) of tea, coffee, cola and/or caffeine-containing beverages within 6 months prior to screening;

Sponsors & Collaborators

• Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.: lead

Study Sites (1)

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Study Officials

• Jing Zhang, Doctor

  Chief technician

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2018
• First Posted: March 8, 2018
• Study Start: March 19, 2018
• Primary Completion: April 23, 2018
• Study Completion: May 8, 2018
• Last Updated: May 30, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)