A Phase 1 interventional study of AZD4831 and Placebo in Cardiovascular Disease, sponsored by AstraZeneca. Completed at 1 site in United States. Open to male participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-01-18.
Sponsored by AstraZeneca · Phase 1, Interventional, and Treatment
This is a Phase I study to investigate the safety and tolerability of AZD4831 in healthy male participants, conducted at a single center. The results from this study will form the basis for decisions on future studies. Another purpose of this dose escalation study is to find out the right dose of the experimental drug to be given to study participants in future studies. Even though there were no harmful effects seen in the animals tested, investigator does not know what side effects the experimental drug might cause in humans. However, site personnel managing the study participants will be blinded to the extent possible and as long as possible to minimize any impact on data collection. Study participants will be blinded to treatment allocation.
The study will be conducted in healthy participants to avoid interference from disease processes or other drugs.
The participants will stay at the study center during the whole dosing period and until 48 hours post final dose.
This is a Phase I study to investigate the safety and tolerability of AZD4831 in healthy male participants, conducted at a single center.The results from this study will form the basis for decisions on future studies. Another purpose of this dose escalation study is to find out the right dose of the experimental drug to be given to study participants in future studies. The study will be conducted in healthy participants to avoid interference from disease processes or other drugs. The participants will stay at the study center during the whole dosing period and until 48 hours post final dose.
4,904 studies on the registry are indexed under Cardiovascular Diseases; 919 are open to participants now.
This study's enrollment of 38 is below the median of 100 across 2,738 interventional studies indexed under Cardiovascular Diseases.
Browse Cardiovascular Diseases studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Any clinically significant abnormalities in biochemistry, hematology, or urinalysis results, as judged by the Investigator at Screening and/or Day 1, including
Abnormal vital signs, after 10 minutes supine rest, at Screening and/or Day 1, defined as any of the following:
Participants will receive AZD4831 5 mg/placebo oral suspension.
Drug: AZD4831 · Drug: Placebo
Participants will receive AZD4831 (Additional dose 1)/placebo oral suspension.
Drug: AZD4831 · Drug: Placebo
Participants will receive AZD4831 (Additional dose 2)/placebo oral suspension.
Drug: AZD4831 · Drug: Placebo
Participants will receive AZD4831 (Additional dose 3)/placebo oral suspension.
Drug: AZD4831 · Drug: Placebo
Participants will receive AZD4831 once daily, orally, for a period of 10 days. Note: Additional doses (for cohorts 2,3\&4) are provisional and could be adjusted based on the emerging data after the review of all available safety or other pertinent data from the previous dose by the Safety Review Committee (SRC).
Participants will receive placebo matching the AZD4831 dose, once daily, orally, for a period of 10 days.
Number of participants with adverse events (AEs)
An AE is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver) or the abnormal results of an investigation (e.g., laboratory findings, ECG).
Time frame: From screening (Day -28 to Day -2) until final follow-up (Day 24)
Systolic Blood pressure
Base line Systolic blood pressure (in mmHg) will be measured at the pre-dose assessment on Day 1. Assessment in treatment period on Day 1 at 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose. On Day 10 at Pre-dose and 12 hours post-dose. On Day 12 at 48 hours post last dose. Measurements will be collected after the subject had rested in the supine position for at least 10 minutes.
Time frame: At screening (Day-28 to Day-2), Day -1, treatment period (Day 1, Day 10 and Day 12) and final follow-up (Day 24)
Twelve lead safety electrocardiography (ECG)
A 12-lead ECG will be performed on Days 1, 2, 3, 6, 10 and 11: (collected at end of dECG recording) and any additional required by PI on Days 4, 5, 7 to 9 at Pre dose and at discharge on Day 12, plus any additional required by PI. A 12-lead ECG will be obtained after the subject rested in the supine position for at least 10 minutes (For time-points coinciding with dECG measurements, a paper printout of the Schiller Cardiovit CS-200 recorder\[ at the end of the 5- or 10-minute dECG recording\], will be used and the result recorded. For time-points not coinciding with dECG measurements, the ECG recording will be directly recorded in ClinBase™ using ClinBase™ Cardiosoft™).
Time frame: At screening (Day-28 to Day-2), treatment period (Day 1 to Day 12), and final follow-up period (Day 24)
Twelve lead digital electrocardiography (dECG)
12-lead continuous dECGs will be recorded over at least 5 minutes on Day 1, 2, 3, 6, 10, 11 \& 12. The AstraZeneca (AZ) ECG Centre will perform the digital ECG (dECG) analysis in this study, using the EClysis© system, version 3.4, or higher. At protocol-indicated time points, 12-lead continuous dECG will be recorded over at least 5 minutes with the Schiller Cardiovit CS-200 recorder (Schiller AG, Baar, Switzerland) and transmitted to the AZ central dECG repository, according to AZ ECG Centre´s standard procedures for settings, recording and transmission of dECGs. Time-points for dECG may be adjusted according to emerging PK data. All ECG recordings will be preceded by a 10-minute controlled rest period.
Time frame: Treatment Period (Day 1 to Day 12)
Telemetry
A 2-lead real-time telemetry ECG will be performed for at least 4 hours on Day -1 and from 30 minutes pre-dose until 24 hours post dose. The telemetry monitoring system will be reviewed by the Investigator or research nurse and paper printouts of any clinically important events will be stored as source data.
Time frame: At Day -1 and treatment period (Day 1 and Day 10)
Hematology
Number of clinically relevant new findings or worsening of a pre-existing findings as assessed by Haematology: Hematocrit (HCT), hemoglobin (Hb), red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell count (WBC), differential blood count (neutrophils, lymphocytes, monocytes, eosinophils and basophils), reticulocytes absolute count, and platelets. Assessments will be performed during treatment period on Day 1 at pre-dose, Day 10 at pre-dose and on Day 12 at 48 hour post final dose before check-out.
Time frame: At screening (Day -28 to Day -2), Day -1, treatment period (Day 1, Day 10 and Day 12), final follow-up (Day 24)
Physical examination
A full physical examination will include the assessment of the following: general appearance, skin, cardiovascular, respiratory, abdomen, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems. A full physical examination will be performed at screening visit and at final follow-up visit (Day 24). A brief physical examination will include assessment of the following: general appearance, skin, cardiovascular system, respiratory and abdomen. A brief physical examination will performed at Day-1, treatment period (Day 1 to Day12) on Day 2: 24 h post first dose, and on Day 12: 48 h post final dose before check-out.
Time frame: At screening (Day-28 to Day-2), Day -1, treatment period (Day 2 and Day 12), and final follow-up period (Day 24)
Diastolic blood pressure
Base line diastolic blood pressure (in mmHg) will be measured at the pre-dose assessment on Day 1. Assessment in treatment period on Day 1 at 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose. On Day 10 at Pre-dose and 12 hours post-dose. On Day 12 at 48 hours post last dose. Measurements will be collected after the subject had rested in the supine position for at least 10 minutes.
Time frame: At screening (Day-28 to Day-2), Day -1, treatment period (Day 1, Day 10 and Day 12) and final follow-up (Day 24)
Pulse rate
Base line pulse rate (in beats per minute (bpm)) will be measured at the pre-dose assessment on Day 1. Assessment in treatment period on Day 1 at 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose. On Day 10 at Pre-dose and 12 hours post-dose. On Day 12 at 48 hours post last dose. Measurements will be collected after the subject had rested in the supine position for at least 10 minutes.
Time frame: At screening (Day-28 to Day-2), Day -1, treatment period (Day 1, Day 10 and Day 12) and final follow-up (Day 24)
Oral body temperature
Oral temperature will be collected after the subject has rested in the supine position for at least 10 minutes.
Time frame: At screening (Day-28 to Day-2), Day-1, treatment period (Day 1 and Day 10 pre-dose)
Biochemistry
Number of clinically relevant new findings or worsening of a pre-existing findings as assessed by serum biochemistry. Electrolytes: Sodium, potassium, calcium, and phosphate. Enzymes: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), high-sensitivity C-reactive protein (hs-CRP). Substrates: Glucose (fasting), creatinine, total bilirubin, unconjugated bilirubin, conjugated bilirubin, albumin, and urea. For serum creatinine testing, blood samples will be collected on Day -1, pre-dose on Day 1, Day 5 and Day 10, follow-up (Day 14, Day 16 and Day 20) and final follow-up (Day 24)
Time frame: At screening (Day -28 to Day -2), Day -1, treatment period (Day 1 pre-dose, Day 10 pre-dose and Day 12 - 48 hours post final dose before check-out) and final follow-up (Day 24)
Urinalysis
Dipstick analysis will be performed at the centre and includes: glucose, creatinine, protein, and blood.
Time frame: At Day -1, treatment period (pre-dose - Day 1, day 5 and Day 10), follow-up (Day 14, day 16 and Day 20) and final follow-up (Day 24)
Microscopy
Microscopy (RBC, WBC and casts \[Hyaline, Granular and Cellular\]) by thermodilatometry (TDL) may be performed at additional urinalysis time points if clinically relevant abnormalities are detected (positive result for protein or blood in dipstick).
Time frame: At Day -1, treatment period (pre-dose - Day 1, day 5 and Day 10), follow-up (Day 14, day 16 and Day 20) and final follow-up (Day 24)
Immunology
Number of clinically relevant new findings or worsening of a pre-existing findings as assessed by Immunology: Anti-neutrophil cytoplasmic antibodies (ANCA - a \& p) testing and complements (C3a, C5a \& Bb). ANCA serum testing will be performed on samples collected on Day -1, pre-dose on Day 1 and on Day 10 and at the final Follow-up Visit (Day 24). Complement testing will be performed on samples collected on Day -1, pre-dose on Day 1, Day 5 and Day 10, follow-up (Day 14, Day 16 and Day 20) and final follow-up (Day 24)
Time frame: At Day -1, treatment period (Day 1 to Day 12), follow-up visits
Observed maximum concentration, taken directly from the individual concentration-time curve(Cmax) of AZD4831 and its metabolites
Observed maximum concentration.
Time frame: Day 1 and Day 10
Time to reach maximum concentration, taken directly from the individual concentration-time curve (tmax) of AZD4831
Time to reach maximum concentration.
Time frame: Day 1 to Day 10
Observed trough plasma concentration [measured concentration at the end of the dosing interval taken just prior to the next administration] (Ctrough) of AZD4831
Observed trough plasma concentration.
Time frame: Day 2 to Day 10
Terminal half-life (t1/2λz), estimated as (ln2)/λz) of AZD4831
Terminal elimination half-life.
Time frame: Day 10
Area under the plasma concentration-curve over 24 hours (AUCτ) of AZD4831
Area under the plasma concentration over 24 hours.
Time frame: Day 1 and Day 10
Area under the plasma concentration-time curve over the dosing interval divided by the dose administered (AUCτ/D) of AZD4831
Area under the plasma concentration-time curve over the dosing interval divided by the dose administered.
Time frame: Day 1 and Day 10
Observed maximum plasma concentration divided by the dose administered (Cmax/D) of AZD4831.
Observed maximum plasma concentration divided by the dose administered.
Time frame: Day 1 and Day 10
Apparent clearance for parent drug (CL/F) estimated as dose divided by AUCτ of AZD4831.
Apparent clearance for parent drug.
Time frame: Day 10
Mean Residence Time (MRT)
Mean Residence Time.
Time frame: Day 10
Apparent volume of distribution for parent drug at terminal phase(Vz/F)(extravascular administration), estimated by dividing the apparent clearance (CL/F) by λz of AZD4831.
Apparent volume of distribution for parent drug at terminal phase.
Time frame: Day 10
Accumulation ratio calculated as AUCτ Day 10/ AUCτ Day 1 (RacAUC) of AZD4831.
Accumulation ratio calculated as AUCτ Day 10/ AUCτ Day 1.
Time frame: Day 10
Accumulation ratio calculated as Cmax Day 10/ Cmax Day 1 (Rac Cmax) of AZD4831.
Accumulation ratio calculated as Cmax Day 10/ Cmax Day 1.
Time frame: Day 10
Amount of analyte excreted into the urine from time t1 to t2 (Ae(t1-t2)) of AZD4831.
Amount of analyte excreted into the urine.
Time frame: Day 1 and Day 10
Cumulative amount of analyte excreted at time t (Ae(0-t)) of AZD4831.
Cumulative amount of analyte excreted at time t.
Time frame: Day 1 and Day 10
Fraction of dose excreted unchanged into the urine from time t1 to t2, estimated by dividing Ae(t1-t2) by dose (fe(t1-t2)) of AZD4831.
Fraction of dose excreted unchanged into the urine.
Time frame: Day 1 and Day 10
Fraction of dose excreted unchanged into the urine from time zero to time t, estimated by dividing Ae(0-t) by dose (fe(0-t)) of AZD4831
Fraction of dose excreted unchanged into the urine.
Time frame: Day 1 and Day 10
Renal clearance, estimated by dividing Ae(0-t) by AUC(0-t), using appropriate matching time t (CLR) of AZD4831.
Renal clearance.
Time frame: Day 1 and Day 10
Terminal rate constant, estimated by log-linear least-squares regression rate constant, estiamteed by log-linear least-squares (λz)
Terminal rate constant
Time frame: Day 10
Plan to share: Undecided
No publications or documents are linked to this record.
This study is completed, as verified in Jan 2020. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
AstraZeneca