Primary:to investigate the effects on heart rate (HR) and rhythm of concomitant administration of the study drug with a calcium-channel blocker (CCB) or a beta-blocker (BB)Secondary:- to investigate the effects on blood pressure (BP) of concomitant…
ID
Source
Brief title
Condition
- Immune disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Cardiodynamics (telemetry)
Pharmacokinetics
Safety
Secondary outcome
n.a.
Background summary
The drug to be given is a new, investigational compound that may eventually be
used for the treatment of immune diseases. The study drug blocks the egress of
lymphocytes from lymphoid organs and reduces the availability of circulating
effector T-cells that can invade target organs and cause immune diseases.
This new compound is not registered as a drug but has been given to humans
before.
In addition also atenolol (beta-blocker) or diltiazem (calcium-channel blocker)
will be given. These are registered drugs which are used for the treatment of
hart-related diseases.
Atenolol is used for the treatment of high blood pressure, angina pectoris
(pain on the chest) and for early intervention at suspicion of acute heart
attack. Diltiazem is used for the treatment of angina pectoris and high blood
pressure.
Study objective
Primary:
to investigate the effects on heart rate (HR) and rhythm of concomitant
administration of the study drug with a calcium-channel blocker (CCB) or a
beta-blocker (BB)
Secondary:
- to investigate the effects on blood pressure (BP) of concomitant
administration of the study drug with a CCB or a BB
- to evaluate the safety and tolerability of concomitant administration of the
study drug with a CCB or a BB
- to evaluate the effects of a CCB or a BB on the pharmacokinetics (PK) of the
study drug
- to evaluate the effects of the study drug on the PK of a CCB or a BB
Study design
Design:
a randomized, open-label, two-part, two-period, two-way crossover study
consisting of two groups of twelve healthy subjects, groups receive either CCB
or BB treatment for six days followed by a single oral dose of the study drug
in one period (design A1 and B1) and a single oral dose of the study drug in
the other period (design A2 and B2) (at least 30% of each sex for each
treatment), a wash-out of 7-10 Days between dosing; treatment scheme Part A:
sequence 1: A1 A2, sequence 2: A2 A1, Part B: sequence 1: B1 B2, sequence 2: B2
B1
Procedures and assessments:
Screening and follow up:
clinical laboratory, physical examination, vital signs, ECG; at eligibility
screening: medical history, drug screen, HBsAg, anti HCV, anti-HIV 1/2 and
pregnancy test (females only); to be repeated upon each admission: vital signs,
ECG, clinical laboratory, drug screen, pregnancy test (females only);
follow-up phone call to check on adverse events: 7 and 30 days after last
study drug administration
Observation period:
one period in clinic from -18 h up to 24 h after drug administration on Day 6
(design A1 and B1)
one period in clinic from -18 h up to 24 h after drug administration on Day 1
(design A2 and B2)
Blood samples:
design A1 and B1:
for pharmacokinetics of atenolol or diltiazem: 24, 48, 72, 96, 97, 98, 99, 100,
101, 102, 103, 104, 106, 108, 110, 120, 121, 122, 123, 124, 125, 126, 127, 128,
130, 132, 134 and 144 h post-dose on Day 1
for pharmacokinetics of the study drug: pre-dose and 1, 2, 3, 4, 6, 10, 14 and
24 h post-dose on Day 6
design A2 and B2:
for pharmacokinetics of the study drug: pre-dose and 1, 2, 3, 4, 6, 10, 14 and
24 h post-dose
Telemetry
design A1 and B1:
interval from 96 * 108 and 120 - 132 h post dose on Day 1
design A2 and B2:
interval from pre-dose - 12 h post dose on Day 1
Safety assessments
design A1 and B1:
adverse events: throughout the study; vital signs and ECG: pre-dose and 1, 2,
3, 4, 24, 48, 72, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108,
110, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 134 and
144 h post-dose on Day 1; physical examination: at discharge; clinical
laboratory: pre-dose and 96, 120 and 144(incl. pregnancy test (females only)) h
post dose on Day 1
design A2 and B2:
adverse events: throughout the study; vital signs and ECG: pre-dose and 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 24 h post dose; physical examination:
at discharge; clinical laboratory: pre-dose and 1 and 24(incl. pregnancy test
(females only)) h post dose
Bioanalysis:
analysis of plasma atenolol samples using a validated method by PRA
analysis of plasma diltiazem samples using a validated method by PRA
analysis of plasma study drug samples using a validated method by Sponsor
Intervention
Active substance: ACT-128800, atenolol, diltiazem extended release
Study burden and risks
Procedures: pain, light bleeding, heamatoma, possibly an infection.
Gewerbestrasse 16
CH-4123 Allschwil
CH
Gewerbestrasse 16
CH-4123 Allschwil
CH
Listed location countries
Age
Inclusion criteria
Age: 18-60 years, inclusive (at screening)
BMI: 18.0-30.0 kg/m2, inclusive;Women of childbearing potential must:
- have a negative serum pregnancy test at screening and prior to first drug intake;
- agree to use two methods of contraception from the screening visit until 2 months after study drug discontinuation.;Systolic blood pressure 100*150 mmHg, diastolic blood pressure 50*90 mmHg measured on the right arm, and HR 55*95 bpm (inclusive)
Exclusion criteria
- Pregnant or lactating woman.
- Known hypersensitivity to any excipients of the study drug formulation
- Known hypersensitivity to atenolol or diltiazem or any of their excipients
- Veins unsuitable for i.v. puncture on either arm
- Treatment with another investigational drug within 3 months prior to screening.
- Excessive caffeine consumption, defined as > 800 mg per day at screening.
- Smoking or nicotine replacement therapy within the last month prior to screening.
- Any immunosuppressive treatment within 6 weeks before study drug administration.
- Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St John*s Wort) within 2 weeks prior to screening or 5 half-lives of the drug, whichever is longer (except for contraceptives).
- Loss of 250 mL or more of blood within 3 months prior to screening.
- Positive hepatitis B surface antigen or hepatitis C antibody tests or positive results for HIV serology, at screening
- Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject*s full participation in the study or compliance with the protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-023248-33-NL |
| CCMO | NL35329.056.11 |