Single ascending dose study of AP30663|
|- candidate number||28532|
|- NTR Number||NTR7012|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||5-feb-2018|
|- Secondary IDs||CHDR1706 |
|- Public Title||Single ascending dose study of AP30663|
|- Scientific Title||Randomized, double-blind, placebo-controlled single ascending dose study to assess the safety and tolerability of AP30663 in healthy subjects|
|- ACRONYM||Single ascending dose study of AP30663|
|- hypothesis||Evaluation of the safety and tolerability of AP3066 in healthy males|
|- Healt Condition(s) or Problem(s) studied||Atrial Fibrillation|
|- Inclusion criteria||1. Signed informed consent prior to any study-mandated procedure |
2. Healthy male subjects, 18 to 45 years of age, inclusive.
3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening, and with a
minimum weight of 50 kg.
4. All male volunteers must practice effective contraception during the study and be willing and
able to continue contraception for at least 90 days after their last dose of study treatment.
5. Has the ability to communicate well with the Investigator in the Dutch language and willing to
comply with the study restrictions.
|- Exclusion criteria||1. Evidence of any active or chronic disease or condition that could interfere with, or for which
the treatment might interfere with, the conduct of the study, or that would pose an
unacceptable risk to the subject in the opinion of the investigator (following a detailed
medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse
rate, body temperature), 12-lead electrocardiogram (ECG), and clinical laboratory
parameters (haematology, blood chemistry, and urinalysis)). Minor deviations of laboratory
values from the normal range may be accepted, if judged by the Investigator or medically
qualified designee as not clinically significant.|
2. Clinically significant abnormalities, as judged by the investigator, in laboratory test results
(including hepatic and renal panels, complete blood count, chemistry panel and urinalysis).
In the case of uncertain or questionable results, tests performed during screening may be
repeated before randomization to confirm eligibility or judged to be clinically irrelevant for
3. Positive Hepatitis B surface antigen (HBsAg), Hepatitis B antibodies, Hepatitis C antibody
(HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
4. Systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and diastolic blood
pressure (DBP) greater than 90 or less than 50 mm Hg at screening.
5. Abnormal findings in the resting ECG at screening defined as:
- QTcF> 450 or < 300 msec
- Notable resting bradycardia (HR < 45 bpm)
- Notable resting tachycardia (HR > 100 bpm)
- Personal or family history of congenital long QT syndrome or sudden death;
- ECG with QRS and/or T wave judged to be unfavorable for a consistently accurate
QT measurement (e.g., neuromuscular artefact that cannot be readily eliminated,
arrhythmias, indistinct QRS onset, low amplitude T wave, merged T- and U-waves,
prominent U waves);
- Evidence of a sustained atrial or ventricular arrhythmia, either by anamnesis or by
Holter or telemetric observation.
- Pre-excitation (Wolff-Parkinson-White syndrome)
- PR interval >220 ms
6. Use of any medications (prescription or over-the-counter [OTC]), within 14 days of
investigational product administration, or less than 5 half-lives (whichever is longer).
Exceptions are paracetamol (up to 4 g/day) and ibuprofen (up to 1g/day). Other exceptions
will only be made if the rationale is clearly documented by the investigator.
7. Use of any vitamin, mineral, herbal, and dietary supplements within 7 days of investigational
product administration, or less than 5 half-lives (whichever is longer). Exceptions will only be
made if the rationale is clearly documented by the investigator.
8. Participation in an investigational product or device study within 3 months prior to first
dosing, or >4 studies in the year prior to study participation.
9. History of abuse of addictive substances (alcohol, illegal substances) or current use of more
than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics,
tranquillizers, or any other addictive agent
10. Positive test for drugs of abuse at screening or pre-dose.
11. Alcohol will not be allowed from at least 24 hours before screening or pre-dose.
12. Current smoker or history of nicotine abuse (average of >5 cigarettes per day for >3 months)
13. Excess in xanthine consumption (more than eight cups of coffee or equivalent per day) or
unwilling or unable to abstain from xanthine consumption during the stay at CHDR.
14. Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or
multiple drug allergies (non-active hay fever is acceptable).
15. Loss or donation of blood over 500 mL within three months (males) prior to screening or
intention to donate blood or blood products during the study.
16. Any known factor, condition, or disease that might interfere with treatment compliance, study
conduct or interpretation of the results such as drug or alcohol dependence or psychiatric
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||2-feb-2018|
|- planned closingdate||1-jun-2018|
|- Target number of participants||48|
|- Interventions||AP30663 and placebo|
|- Primary outcome||Tolerability / safety endpoints|
• Occurrence of all treatment-related AEs;
• Changes in vital signs, temperature, laboratory safety data and ECGs between pre-first infusion and each post-infusion time point;
• Changes in tremorography data;
• Changes in physical examination findings.
• Maximum observed plasma concentration (Cmax) for each cohort.
• Time to maximum observed plasma concentration (tmax) for each cohort.
• Area under the plasma concentration-time curve (AUC) for each dosing group (area under the plasma concentration-time curve from time zero to infinity [AUCinf],area under the plasma concentration-time curve from time zero to time of last measurable concentration [AUCtlast], area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC [AUC%extrapolated]) for each cohort.
• Apparent clearance (CL), apparent volume of distribution during terminal phase (Vz) and apparent volume of distribution at steady state (Vss) and half-life (t½) for each cohort.
• Based on ECG data, the following pharmacodynamic endpoints are deployed:
- RR interval
- PQ, QRS, QT/QTcF interval duration
- P, P', QRS, QRS', T, T' wave duration, amplitude and area
- R axis
- Atrial and ventricular ectopic beats on Holter recording
|- Secondary outcome||N.A.|
|- Timepoints||Day -1 until Day 8|
|- Trial web site||www.CHDR.nl|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. J. Burggraaf|
|- CONTACT for SCIENTIFIC QUERIES||MD. J. Burggraaf|
|- Sponsor/Initiator ||Acesion Pharma ApS |
(Source(s) of Monetary or Material Support)
|Acesion Pharma ApS|
|- Publications||To be published|
|- Brief summary||The study will be conducted in the Netherlands .|
Atrial fibrillation (AF) can be an invalidating arrhythmia, with frequent recurrences requiring pharmacological or electrical cardioversion. Current medical maintenance or ablative procedures are hampered by not infrequent therapy failures. Additionally, pharmacological cardioversion with currently available treatment options is unsuccessful in many patients, predominantly patients with persistent AF.
AP30663 is a first in class compound targeted at cardioversion of both paroxysmal and persistent AF. The compound inhibits the small conductance Ca2+ activated K+ channels (SK channels). These channels are associated with a prolongation of the effective refractory period (ERP) of atrial myocardial cells both in vitro and in vivo.
The current study is a first-in-man study in healthy volunteers, in which AP30663 is administered to assess the safety and tolerability.
|- Main changes (audit trail)|
|- RECORD||5-feb-2018 - 18-feb-2018|
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