Atrial FibrillationPhase 1NCT03397641

A Phase 1 Study of HBI-3000

A Phase 1 study testing HBI-3000 in people with Atrial Fibrillation, run by HUYABIO International, LLC. at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Atrial Fibrillation
What is being tested?: HBI-3000
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 47 participants
Where: 1 siteUnited Kingdom
Study dates: 17 Oct 2017to 10 Jul 2018
Phase: Phase 1
Are there results?: None posted in the registry

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 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy males or non-pregnant, non-lactating healthy females
Age 18 to 50 years
Body mass index of 18.0 to 30.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
Minimum body weight of 60 kg
Must be willing and able to communicate and participate in the whole study
Normal hepatic function as evidenced by AST and alanine aminotransferase (ALT) <1.5 × ULN and alkaline phosphatase (ALP) and total bilirubin within the normal range

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Haemodynamically stable with systolic BP 90 to 150 mm Hg, diastolic BP <95 mmHg and resting HR ≥45 and ≤100 bpm
Forced expiratory volume in 1 s (FEV1) >80% predicted value and FEV1/ forced vital capacity (FVC) ratio >0.7
Must provide written informed consent
Must agree to use an adequate method of contraception

Who cannot join

Subjects who have received any IMP in a clinical research study within the previous 3 months
Subjects who are study site employees, or immediate family members of a study site or sponsor employee
Subjects who have previously been enrolled in this study.
History of any drug or alcohol abuse in the past 2 years
Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening

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Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
Females of childbearing potential who are pregnant or lactating (all female subjects must have a negative pregnancy test). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration ≥40 IU/L)
Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis as judged by the investigator, including:
Serum K <3.5 mmol/L
Serum magnesium concentration of <0.7 mmol/L
Serum phosphate <2.5 or >4.5 mg/dL
Positive drugs of abuse test result
Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <80 mL/min using the Cockcroft-Gault equation
Evidence of any clinically relevant acute or chronic medical illness, including renal, hepatic, haematological, endocrine, pulmonary (including asthma), oncologic, neurologic or gastrointestinal disease, or psychiatric disorder, as judged by the investigator
History or presence of clinically significant cardiovascular disease, including coronary artery disease, myocardial infarction or ischemia, congestive heart failure, valvular disease, congenital heart disease or prior cardiac surgery
History or presence of cardiac arrhythmia or conduction abnormalities, including long-QT syndrome, TdeP, Wolff-Parkinson-White syndrome or bradycardia (<45 bpm)
QTcF interval >450 or QRS >120 msec
Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active
Donation or loss of greater than 400 mL of blood within the previous 3 months
Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 g per day paracetamol and HRT/hormonal contraception) or herbal remedies in the 14 days before IMP administration (see Section 11.4). Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor.
Failure to satisfy the investigator of fitness to participate for any other reason

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Quotient Clinical
Nottingham, NG11 6JS

Other trials in United Kingdom

About this study

Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Serial Cohort Dose-Escalation Study of Intravenously Administered HBI-3000

This is a Phase 1 randomised, double-blind, placebo-controlled, serial cohort, dose-escalation study in healthy adult volunteers. It is planned to enroll 5 cohorts (Cohorts A to E) of 8 subjects. Up to 2 additional cohorts (Cohorts F and G) may be enrolled as needed to establish the safety profile of HBI-3000 over a clinically relevant range of doses. Subjects will be randomly assigned to receive a single dose of HBI-3000 or matching placebo in a sequential escalating manner (Regimens A to E and optional Regimens F and G), with a minimum of 7 days and a maximum based on logistics of interim review between dose groups.

As a safety precaution, in each cohort a sentinel dosing group of n = 2 (1 active:1 placebo) will be dosed at least 24 h ahead of the main group. Safety and tolerability will be assessed by the principal investigator or medically-qualified designee before continuing with dosing the remaining subjects. The first 2 subjects will be allocated to active or placebo in a 1:1 ratio. The remaining 6 subjects will be allocated to active or placebo in a 5:1 ratio.

Doses of HBI-3000 may range from 20 mg to a level at which it is expected that the drug exposure will not exceed an AUC(0-t) of 20 μg.h/mL and Cmax of 20 μg/mL (based on the no-observed-adverse-effect levels [NOAEL] in both 14 day repeat dose toxicology species the rat and minipig) and the expected therapeutic dose range. Following administration to each cohort, there will be an interim data review during which the PK and safety data will be reviewed to determine the dose to be administered in the next cohort. Dose escalation for serial cohorts will progress unless safety concerns preclude further dose escalation. If the selected dose does not provide the required data, a previously tested dose may be used in a subsequent cohort. However, if the dose level met the dose escalation stopping criteria, that dose level must not be repeated. A previously untested intermediate dose may also be used in a subsequent cohort.

Conditions: Atrial Fibrillation
Being tested: HBI-3000, Placebo
Medical subject headings: Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

HBI-3000Drug
Also called Sulcardine sulfate
Small molecule, multi-ion channel blocker
PlaceboOther
Normal Saline

Study groups in NCT03397641
Study group	Role	What they receive
Active	Active comparator	x mg HBI-3000 as x mL of a 50 mg/mL solution for intravenous infusion. Doses of HBI-3000 (Cohorts A to G) may range from 20 mg to a level at which it is expected that the drug exposure will not exceed an AUC(0-t) of 20 µg.h/mL and Cmax of 20 µg/mL (based on the NOAEL) in both 14-day repeat-dose toxicology species rat and minipig) and the expected therapeutic dose. Receives: Drug: HBI-3000
Placebo	Placebo comparator	Matching placebo for x mg HBI-3000 as x mL of a 50 mg/mL solution for intravenous infusion. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Physical Examination (Safety and Tolerability)
Typical physical examination, including general appearance; head, neck, and thyroid; ears, nose, and throat; cardiovascular; respiratory; lymph nodes; abdomen; dermatological; musculoskeletal; neurological/CNS; ocular/ophthalmology; and other (as specified) evaluation
Measured: Change from screening (3 to 28 d prior to dosing), admission (2 d prior to dosing), 48 h post-start of infusion, and 7 d +/- 1 d post-start of infusion (follow-up visit)
Safety Labs (Safety and Tolerability)
Hematology (hemoglobin[g/L], HCT[%], RBC[x10^12/L], MCV[fL], MCH[pg], MCHC[g/L], platelet[x10^9/L], WBC[x10^9/L], neutrophils[x10^9/L], lymphocytes[x10^9/L], monocytes[x10^9/L], eosinophils[x10^9/L], basophils[x10^9/L], hematocrit[%]), coagulation (prothrombin time[s], APTT[s]), clinical chemistry (Na[mmol/L], K[mmol/L], Cl[mmol/L], bicarbonate[mmol/L], urea[mmol/L], creatinine[µmol/L], bilirubin[µmol/L], direct conj bilirubin[µmol/L], alkaline phosphatase[IU/L], aspartate aminotransferase[IU/L], alanine aminotransferase[IU/L], creatinine kinase[IU/L], gamma glutamyl transferase[IU/L], total protein[g/L], albumin[g/L], Ca[mmol/L], Mg[mmol/L], P[mmol/L], uric acid[µmol/L], random blood glucose[mmol/L], fasting blood glucose[mmol/L], triglycerides[mmol/L], fasting triglycerides[mmol/L], creatinine clearance[mL/min]), virology (Hepatitis B surface[+/-], Antigen[+/-], Hepatitis C[+/-], Antibody[+/-], HIV Antibody[+/-]); and FSH(IU/L) and beta H.C.G. serum(+/-)
Measured: Change from screening (3 to 28 d prior to dosing), 1 d prior to dosing, 24 h and 48 h post-start of infusion, and 7 d +/- 1 d post-start of infusion (follow-up visit)
Urinalysis (Safety and Tolerability)
Bilirubin (-/+; +, ++, +++), urobilinogen (-/+; 2, 4, 8, 12 mg/dL), ketones (-/+; trace, +, ++, +++), glucose (-/+; 50, 100, 250, 500, ≥1000 mg/dL), pH (5.0, 6.0, 6.5, 7.0, 8.0, 9.0), hCG (female subjects; -/+), specific gravity (1.000, 1.005, 1.010, 1.015, 1.020, 1.025, 1.030), protein (-/+; trace, 30, 100, 500 mg/dL), blood (-/+; +ca.5-10, ++ca.50, +++ca.300, ca.5-10, ca.50, ca.300 ery/µL), nitrites (-/+; light pink, dark pink), leukocytes (-/+; ca.25, ca.75, ca.500 leuko/µL) (performed using dipsticks; if positive, tick correct result), microbiology (WBS [HPF], RBCS [HPF], hyaline casts [HPF], granular casts [HPF], cellular casts [HPF]) and urine microscopy (both at the discretion of the investigator based on urinalysis results), and drugs of abuse (amphetamines [+/-], barbiturates [+/-], benzodiazepines [+/-], cocaine [+/-], marijuana/cannabis [+/-], methadone [+/-], methamphetamine/ecstasy [+/-], morphine/opiates [+/-], phencyclidine [+/-], tricyclic antidepressants [+/-])
Measured: Change from screening (3 to 28 d prior to dosing), admission (2 d prior to dosing), 24 h and 48 h post-start of infusion, and 7 d +/- 1 d post-start of infusion (follow-up visit)
Pulmonary Function Tests (Safety and Tolerability)
The following lung function tests will be performed using a standard calibrated spirometer: FEV1 (L), FVC (L), peak expiratory flow rate (PEFR) (L/min), and FEV1/FVC (%)
Measured: Change from screening (3 to 28 d prior to dosing), pre-dose (within 24 h prior to dosing), and 0.75 h and 4 h post-start of infusion
12-Lead ECG (Safety and Tolerability)
Measured after subject has been in supine position for at least 5 min.
Measured: Change from screening (3 to 28 d prior to dosing), admission (2 d prior to dosing), pre-dose (within 24 h prior to dosing), 0.25 h, immediately prior to end of infusion, 1, 4, 6, 12, 24, and 48 h, and 7 d +/- 1 d post-start of infusion
Holter ECG (Safety and Tolerability)
Continuous ECG monitoring; subjects to be in supine position for at least 0.25 h before each extraction
Measured: Data extractions on Day -1 will be time matched to the planned time of dosing on Day 1 (i.e., 12 extractions); the extraction time points on Day 1 are: pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-start of infusion
Telemetry ECG (Safety and Tolerability)
No data are collected (safety monitoring); if cardiac monitoring shows a potentially significant abnormality, a clinical assessment of the subject will be performed, including a 12-lead ECG, and treatment given.
Measured: To commence approximately 10 min before dosing up to 6 h post-start of infusion
Vital Signs (Safety and Tolerability)
Blood pressure (mmHg), heart rate (bpm), oral temperature (degrees C or degrees F)
Measured: Change from screening (3 to 28 d prior to dosing), admission (2 d prior to dosing), pre-dose (within 24 h prior to dosing), 0.25 h, immediately prior to end of infusion, 1, 2, 4, 6, 8, 12, 16, 24, 30, 36, and 48 h, and 7 d +/- 1 d post-start of infusion
Adverse Events (Safety and Tolerability)
All AEs are documented, including the date and time of onset, a description of the AE, severity, duration, actions taken, outcome and investigator's current opinion on the relationship between HBI-3000 and the event.
Measured: 0.25 h post-start of infusion through 7 d +/- 1 d post-start of infusion (follow-up visit)

Secondary outcomes (17)

HBI-3000 Levels Over Time in Plasma (Cmax)
Peak Plasma Concentration, Cmax (µg/mL)
Measured: Change in Cmax from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (Tmax)
Time to Reach the Peak Plasma Concentration, Tmax (h)
Measured: Change in Tmax from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (AUC(0-last))
Area Under the Plasma Concentration versus Time Curve from Time Zero to Time of Last Measurable Concentration, AUC(0-last) (µg·h/mL)
Measured: Change in AUC(0-last) from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (AUC(0-inf))
Area Under the Plasma Concentration versus Time Curve from Time Zero to Infinity, AUC(0-inf) (µg·h/mL)
Measured: Change in AUC(0-inf) from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (AUC(0-24h))
Area Under the Plasma Concentration versus Time Curve from Time Zero to Time 24h, AUC(0-24h) (µg·h/mL)
Measured: Change in AUC(0-24h) from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (AUC%extrap)
Area Under the Plasma Concentration versus Time Curve Extrapolated from Time t to Infinity as a Percentage of total AUC, AUC%extrap (%)
Measured: Change in AUC%extrap from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (lambda-z)
Terminal Disposition Rate Constant/Terminal Rate Constant, lambda-z (1/h)
Measured: Change in lambda-z from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (T1/2)
Elimination Half Life, T1/2 (h)
Measured: Change in T1/2 from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (CL)
Apparent Total Clearance of the Drug from Plasma, CL (mL/h·kg)
Measured: Change in CL from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (CLr)
Renal Clearance of the Drug from Plasma, CLr (mL/h·kg)
Measured: Change in CLr from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (Vz)
Apparent Volume of Distribution during Terminal Phase, Vz (L/kg)
Measured: Change in Vz from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (Vss)
Apparent Volume of Distribution at Steady State, Vss (L/kg)
Measured: Change in Vss from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (MRT)
Mean Residence Time, MRT (h)
Measured: Change in MRT from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Urine (Ae)
Amount of Unchanged Drug Excreted into the Urine, Ae (µg)
Measured: Change in Ae from pre-dose (within 24 h prior to dosing), and 0-6 h, 6-12 h, 12-24 h post-start of infusion
HBI-3000 Levels Over Time in Urine (CumAe)
Cumulative Recovery of Unchanged Drug Excreted into the Urine, CumAe (µg)
Measured: Change in CumAe from pre-dose (within 24 h prior to dosing), and 0-6 h, 6-12 h, 12-24 h post-start of infusion
HBI-3000 Levels Over Time in Urine (%Ae)
Amount of Unchanged Drug Excreted into the Urine as a Percentage of the Administered Dose, %Ae (%)
Measured: Change in %Ae from pre-dose (within 24 h prior to dosing), and 0-6 h, 6-12 h, 12-24 h post-start of infusion
HBI-3000 Levels Over Time in Urine (Cum%Ae)
Cumulative Recovery of Unchanged Drug Excreted into the Urine as a Percentage of the Dose, Cum%Ae (%)
Measured: Change in Cum%Ae from pre-dose (within 24 h prior to dosing), and 0-6 h, 6-12 h, 12-24 h post-start of infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Oct 201710 Jul 2018

First posted12 Jan 2018
Study start17 Oct 2017
Primary completion10 Jul 2018
Study completion10 Jul 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Atrial FibrillationStudies 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: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03397641
Sponsor's protocol ID: HBI-3000-301
Other IDs: 2017-003642-24, 2017
Status last verified: Aug 2018
First submitted: 28 Nov 2017
Last updated: 29 Aug 2018
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Serial Cohort Dose-Escalation Study of Intravenously Administered HBI-3000
ClinicalTrials.gov ID: NCT03397641
Acronym / sponsor ID: HBI-3000-301
Conditions: Atrial Fibrillation
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 47 participants (actual)
Lead sponsor: HUYABIO International, LLC.Industry (pharma, biotech, devices)
Collaborators: Quotient Clinical
Study start: 17 Oct 2017 (actual)
Primary completion: 10 Jul 2018 (actual)
Study completion: 10 Jul 2018 (actual)
First posted: 12 Jan 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Active	Active comparator	Drug: HBI-3000x mg HBI-3000 as x mL of a 50 mg/mL solution for intravenous infusion. Doses of HBI-3000 (Cohorts A to G) may range from 20 mg to a level at which it is expected that the drug exposure will not exceed an AUC(0-t) of 20 µg.h/mL and Cmax of 20 µg/mL (based on the NOAEL) in both 14-day repeat-dose toxicology species rat and minipig) and the expected therapeutic dose.
Placebo	Placebo comparator	Other: PlaceboMatching placebo for x mg HBI-3000 as x mL of a 50 mg/mL solution for intravenous infusion.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (10 listed)

Healthy males or non-pregnant, non-lactating healthy females
Age 18 to 50 years
Body mass index of 18.0 to 30.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
Minimum body weight of 60 kg
Must be willing and able to communicate and participate in the whole study

Key exclusion criteria (25 listed)

Subjects who have received any IMP in a clinical research study within the previous 3 months
Subjects who are study site employees, or immediate family members of a study site or sponsor employee
Subjects who have previously been enrolled in this study.
History of any drug or alcohol abuse in the past 2 years
Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
HBI-3000Also: Sulcardine sulfateSmall molecule, multi-ion channel blocker	Drug	Active
PlaceboNormal Saline	Other	Placebo

Primary outcome

Physical Examination (Safety and Tolerability)
Time frame: Change from screening (3 to 28 d prior to dosing), admission (2 d prior to dosing), 48 h post-start of infusion, and 7 d +/- 1 d post-start of infusion (follow-up visit)
Typical physical examination, including general appearance; head, neck, and thyroid; ears, nose, and throat; cardiovascular; respiratory; lymph nodes; abdomen; dermatological; musculoskeletal; neurological/CNS; ocular/ophthalmology; and other (as specified) evaluation
Safety Labs (Safety and Tolerability)
Time frame: Change from screening (3 to 28 d prior to dosing), 1 d prior to dosing, 24 h and 48 h post-start of infusion, and 7 d +/- 1 d post-start of infusion (follow-up visit)
Hematology (hemoglobin[g/L], HCT[%], RBC[x10^12/L], MCV[fL], MCH[pg], MCHC[g/L], platelet[x10^9/L], WBC[x10^9/L], neutrophils[x10^9/L], lymphocytes[x10^9/L], monocytes[x10^9/L], eosinophils[x10^9/L], basophils[x10^9/L], hematocrit[%]), coagulation (prothrombin time[s], APTT[s]), clinical chemistry (Na[mmol/L], K[mmol/L], Cl[mmol/L], bicarbonate[mmol/L], urea[mmol/L], creatinine[µmol/L], bilirubin[µmol/L], direct conj bilirubin[µmol/L], alkaline phosphatase[IU/L], aspartate aminotransferase[IU/L], alanine aminotransferase[IU/L], creatinine kinase[IU/L], gamma glutamyl transferase[IU/L], total protein[g/L], albumin[g/L], Ca[mmol/L], Mg[mmol/L], P[mmol/L], uric acid[µmol/L], random blood glucose[mmol/L], fasting blood glucose[mmol/L], triglycerides[mmol/L], fasting triglycerides[mmol/L], creatinine clearance[mL/min]), virology (Hepatitis B surface[+/-], Antigen[+/-], Hepatitis C[+/-], Antibody[+/-], HIV Antibody[+/-]); and FSH(IU/L) and beta H.C.G. serum(+/-)
Urinalysis (Safety and Tolerability)
Time frame: Change from screening (3 to 28 d prior to dosing), admission (2 d prior to dosing), 24 h and 48 h post-start of infusion, and 7 d +/- 1 d post-start of infusion (follow-up visit)
Bilirubin (-/+; +, ++, +++), urobilinogen (-/+; 2, 4, 8, 12 mg/dL), ketones (-/+; trace, +, ++, +++), glucose (-/+; 50, 100, 250, 500, ≥1000 mg/dL), pH (5.0, 6.0, 6.5, 7.0, 8.0, 9.0), hCG (female subjects; -/+), specific gravity (1.000, 1.005, 1.010, 1.015, 1.020, 1.025, 1.030), protein (-/+; trace, 30, 100, 500 mg/dL), blood (-/+; +ca.5-10, ++ca.50, +++ca.300, ca.5-10, ca.50, ca.300 ery/µL), nitrites (-/+; light pink, dark pink), leukocytes (-/+; ca.25, ca.75, ca.500 leuko/µL) (performed using dipsticks; if positive, tick correct result), microbiology (WBS [HPF], RBCS [HPF], hyaline casts [HPF], granular casts [HPF], cellular casts [HPF]) and urine microscopy (both at the discretion of the investigator based on urinalysis results), and drugs of abuse (amphetamines [+/-], barbiturates [+/-], benzodiazepines [+/-], cocaine [+/-], marijuana/cannabis [+/-], methadone [+/-], methamphetamine/ecstasy [+/-], morphine/opiates [+/-], phencyclidine [+/-], tricyclic antidepressants [+/-])
Pulmonary Function Tests (Safety and Tolerability)
Time frame: Change from screening (3 to 28 d prior to dosing), pre-dose (within 24 h prior to dosing), and 0.75 h and 4 h post-start of infusion
The following lung function tests will be performed using a standard calibrated spirometer: FEV1 (L), FVC (L), peak expiratory flow rate (PEFR) (L/min), and FEV1/FVC (%)
12-Lead ECG (Safety and Tolerability)
Time frame: Change from screening (3 to 28 d prior to dosing), admission (2 d prior to dosing), pre-dose (within 24 h prior to dosing), 0.25 h, immediately prior to end of infusion, 1, 4, 6, 12, 24, and 48 h, and 7 d +/- 1 d post-start of infusion
Measured after subject has been in supine position for at least 5 min.
Holter ECG (Safety and Tolerability)
Time frame: Data extractions on Day -1 will be time matched to the planned time of dosing on Day 1 (i.e., 12 extractions); the extraction time points on Day 1 are: pre-dose, 0.25 h, 0.5 h, 0.75 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, and 24 h post-start of infusion
Continuous ECG monitoring; subjects to be in supine position for at least 0.25 h before each extraction
Telemetry ECG (Safety and Tolerability)
Time frame: To commence approximately 10 min before dosing up to 6 h post-start of infusion
No data are collected (safety monitoring); if cardiac monitoring shows a potentially significant abnormality, a clinical assessment of the subject will be performed, including a 12-lead ECG, and treatment given.
Vital Signs (Safety and Tolerability)
Time frame: Change from screening (3 to 28 d prior to dosing), admission (2 d prior to dosing), pre-dose (within 24 h prior to dosing), 0.25 h, immediately prior to end of infusion, 1, 2, 4, 6, 8, 12, 16, 24, 30, 36, and 48 h, and 7 d +/- 1 d post-start of infusion
Blood pressure (mmHg), heart rate (bpm), oral temperature (degrees C or degrees F)
Adverse Events (Safety and Tolerability)
Time frame: 0.25 h post-start of infusion through 7 d +/- 1 d post-start of infusion (follow-up visit)
All AEs are documented, including the date and time of onset, a description of the AE, severity, duration, actions taken, outcome and investigator's current opinion on the relationship between HBI-3000 and the event.

17 secondary outcomes

HBI-3000 Levels Over Time in Plasma (Cmax)
Time frame: Change in Cmax from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (Tmax)
Time frame: Change in Tmax from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (AUC(0-last))
Time frame: Change in AUC(0-last) from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (AUC(0-inf))
Time frame: Change in AUC(0-inf) from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (AUC(0-24h))
Time frame: Change in AUC(0-24h) from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (AUC%extrap)
Time frame: Change in AUC%extrap from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (lambda-z)
Time frame: Change in lambda-z from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (T1/2)
Time frame: Change in T1/2 from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (CL)
Time frame: Change in CL from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (CLr)
Time frame: Change in CLr from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (Vz)
Time frame: Change in Vz from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (Vss)
Time frame: Change in Vss from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Plasma (MRT)
Time frame: Change in MRT from pre-dose (within 24 h prior to dosing), and 0.25 h, immediately prior to end of infusion, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 30 h, 36 h, 48 h, 72 h post-start of infusion
HBI-3000 Levels Over Time in Urine (Ae)
Time frame: Change in Ae from pre-dose (within 24 h prior to dosing), and 0-6 h, 6-12 h, 12-24 h post-start of infusion
HBI-3000 Levels Over Time in Urine (CumAe)
Time frame: Change in CumAe from pre-dose (within 24 h prior to dosing), and 0-6 h, 6-12 h, 12-24 h post-start of infusion
HBI-3000 Levels Over Time in Urine (%Ae)
Time frame: Change in %Ae from pre-dose (within 24 h prior to dosing), and 0-6 h, 6-12 h, 12-24 h post-start of infusion
HBI-3000 Levels Over Time in Urine (Cum%Ae)
Time frame: Change in Cum%Ae from pre-dose (within 24 h prior to dosing), and 0-6 h, 6-12 h, 12-24 h post-start of infusion

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2018.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stuart Mair study director

Quotient Clinical

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HBI-3000 in people with Atrial Fibrillation, run by HUYABIO International, LLC. at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Physical Examination (Safety and Tolerability) (time frame: Change from screening (3 to 28 d prior to dosing), admission (2 d prior to dosing), 48 h post-start of infusion, and 7 d +/- 1 d post-start of infusion (follow-up visit)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03397641.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2018.