The primary objectives are:* to determine the effect of steady-state concentrations of TMC114 coadministered with a lowdose of ritonavir on the steady-state pharmacokinetics of ddI,* to determine the effect of steady-state concentrations of ddI on…
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Farmacokinetic blood-and urine investigation
Secondary outcome
Safety and tolerability
Background summary
The new investigational drug called TMC114 is in process of development for the
treatment of people who are infected with the Human Immunodeficiency Virus-Type
1 (HIV-1). TMC114 belongs to a group of medications called protease inhibitors
(PIs) used in the treatment of HIV infection. Ritonavir, another protease
inhibitor, is a prescription drug used in the treatment of infected subjects
with the HIV-1 virus and is often given at a low dose in combination with other
protease inhibitors. The co-administration of ritonavir results in more
favorable concentrations of
TMC114 in the blood and better tolerability. Didanosine (ddI) - which can be
given in combination with TMC114/ritonavir - is also a prescription drug used
in the treatment of patients infected with the HIV-1 virus. ddI is a synthetic
purine nucleoside analogue active against HIV-1 virus.
Study objective
The primary objectives are:
* to determine the effect of steady-state concentrations of TMC114
coadministered with a low
dose of ritonavir on the steady-state pharmacokinetics of ddI,
* to determine the effect of steady-state concentrations of ddI on the
steady-state
pharmacokinetics of TMC114 coadministered with a low dose of ritonavir.
The secondary objective is
* to evaluate the short-term safety and tolerability of the concomitant use of
TMC114, lowdose
ritonavir and ddI.
Study design
This is a Phase I, open label, randomized, 3-way crossover trial in healthy
subjects to investigate the pharmacokinetic interaction between ddI and TMC114,
in combination with a low dose of ritonavir, at steady-state. The study
population will consist of 18 healthy subjects. In 3 sessions, each subject
will receive 600/100 mg TMC114/rtv b.i.d. (Treatment A), 400 mg ddI q.d.
(Treatment B), and a combination of 600/100 mg TMC114/rtv b.i.d. and 400 mg ddI
q.d. (Treatment C).
Treatment A will be administered for 6 days with an additional morning dose on
Day 7.
Treatments B and C will be administered for 7 days. Subsequent sessions will be
separated by a washout period of at least 7 days. ddI should be taken on an
empty stomach, TMC114/rtv should be taken under fed conditions (and 2 hours
after ddI intake during the coadministration phase).
Full pharmacokinetic profiles will be determined for one dosing interval after
the morning intake on Day 7 of Treatment A and C for TMC114 and ritonavir, and
of Treatment B and C for ddI.
The short-term safety and tolerability will also be assessed.
Intervention
Treatment Dose Volume
A --> 2 tablets TMC114 and 1 capsule ritonavir b.i.d.
B --> 1 capsule didanosine q.d.
C --> 2 tablets TMC114, 1 capsule ritonavir b.i.d.
1 capsule didanosine q.d.
Study burden and risks
The risks of participation in this trial is associated with possible adverse
events of TMC114, ritonavir and didanosine. The burden for the participant is
also associated with the admission to the unit, venapunction and insertion of
canule. All subjects will be carefully followed on any adverse events and will
be under the supervision of experienced physicians and study personnel.
Generaal De Wittelaan L11 B3
2800 Mechelen
Nederland
Generaal De Wittelaan L11 B3
2800 Mechelen
Nederland
Listed location countries
Age
Inclusion criteria
1. Male or female subjects, aged between 18 and 55 years, extremes included.
2. Non-smoking or smoking no more than 10 cigarettes, or 2 cigars, or 2 pipes per day for at least 3 months prior to selection.
3. Normal weight as defined by a Quetelet Index (Body Mass Index: weight in kg divided by the square of height in meters) of 18.0 to 30.0 kg/m2, extremes included17 (and of a minimum weight of 60 kg).
4. Informed Consent Form (ICF) signed voluntarily before the first trial-related activity.
5. Able to comply with protocol requirements.
6. Healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes physical examination (including skin examination), medical history, electrocardiogram, vital signs and the results of blood biochemistry, hematology and blood coagulation tests and a urinalysis carried out at screening.
Exclusion criteria
- History or evidence of current use of alcohol
- A positive urine drug test at screening
- Participation in an investigational drug trial within 90 days prior to the first intake of trial medication
- Having previously participated in a multiple-dose trial with TMC114
- Having previously participated in more than one single-dose trial with TMC114
- Blood or plasma drawn or donated within 60 days prior to the screening visit
- A positive HIV-1 or HIV-2 test at study screening
- Hepatitis A, B or C infection
- A positive pregnancy test or breast feeding at screening
- History of significant drug allerby such as, but not limited to, sulfonamides and penicillines
- Use of concomitant medication, including over-the-counter products and dietary supplements. All concomitant medication must have been discontinued at least 14 days prior to the first intake of trial medication, except for paracetamol (acetaminophen), which may be used up to 3 days before the first dose of trial medication
- Not suitable to participate in the trial according to the opinion of the investigator
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 | EUCTR2006-001592-38-NL |
| CCMO | NL12610.040.06 |