Single dose:The objectives of Part 1 (single dose escalation part) are to examine the safety, tolerability and pharmacokinetics (i.e., the circulating levels of TMC558445 in your blood over time) of increasing single oral doses of TMC558445, with…
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Single dose:
The objectives are to examine the safety, tolerability and pharmacokinetics
(i.e., the circulating levels of TMC558445 in your blood over time) of
increasing single oral doses of TMC558445, with and without food.
Multiple dose:
The objectives of Part 2 (multiple dose escalation part) are to examine the
safety, tolerability and pharmacokinetics of increasing repeated oral doses of
TMC558445, followed by a single dose of TMC558445 together with TMC310911 or
DRV to assess whether the combined intake of TMC558445 with TMC310911 or DRV
increases the circulating levels of TMC310911 or DRV in blood.
Secondary outcome
Not applicable.
Background summary
In this study 2 investigational new drugs and 1 registrated drug are involved.
The 2 new investigational drugs called TMC558445 (from the PEPI family) and
TMC310 911 are in process of development for the treatment of Human
Immunodeficiency Virus-Type 1 (HIV-1). TMC558445 and TMC310911 are both being
developed by Tibotec Pharmaceuticals are not approved for use by the US Food
and Drug Administration and other Regulatory Authorities in the European Union
(EU). Therefore, they can only be used in a research study.
TMC558445 is a novel molecule with no antiviral activity to be used to enhance
the pharmacokinetics profile of a drug. TMC310911 is a novel and potent
compound and belongs to a medication class called protease inhibitors (PI). It
is assumed to be very active against the HIV-1 virus, the virus that causes
AIDS, when other treatments will fail.
TMC114 (darunavir) is a new-generation inhibitor of the Human Immunodeficiency
Virus (HIV) protease (an enzyme), marketed under the name of Prezista, and used
worldwide to treat patients with HIV-1 infection. TMC114 is approved and
commercially available for both treatment experienced (600 mg twice daily) and
naïve (800 mg once daily) HIV-infected patients when co administered with low
dose of ritonavir (100 mg twice or once daily, respectively) as a
pharmacokinetic enhancer. TMC114 is the company's reference standard protease
inhibitor and will serve as a comparator for boosting efficacy with TMC558445.
More than 3,000 HIV-1 infected subjects have been treated so far with
TMC114/rtv in studies in humans. Many of these subjects received TMC114 for at
least 1 year. Additionally, approximately 1,300 healthy volunteers have
received TMC114 for a period of 1 day up to 2 weeks in studies in humans. The
safety of use of TMC114 is well documented and the potential unwanted side
effects are summarized below.
Study objective
Single dose:
The objectives of Part 1 (single dose escalation part) are to examine the
safety, tolerability and pharmacokinetics (i.e., the circulating levels of
TMC558445 in your blood over time) of increasing single oral doses of
TMC558445, with and without food.
Multiple dose:
The objectives of Part 2 (multiple dose escalation part) are to examine the
safety, tolerability and pharmacokinetics of increasing repeated oral doses of
TMC558445, followed by a single dose of TMC558445 together with TMC310911 or
DRV to assess whether the combined intake of TMC558445 with TMC310911 or DRV
increases the circulating levels of TMC310911 or DRV in blood.
Study design
The study has a randomized, double blind, placebo-controlled design.
Intervention
Single dose:
Will consist of 6 sessions (Sessions I to VI). Nine subjects will take part in
Sessions I, III and V (Panel 1), and 9 other subjects take part in Sessions II,
IV and VI (Panel 2). In each session, 6 subjects will take TMC558445 and 3
subjects will take placebo. Over 3 sessions, each subject will receive
TMC558445 twice and placebo once.
After completion of Sessions I to VI, 9 subjects (either from Panel 1 or Panel
2, depending on the chosen dose) will have an additional session (Session VII)
to investigate a possible effect of food. The dose of TMC558445 will be a dose
chosen out of the 6 previously administered doses of Panels 1 or 2. Subjects
who received TMC558445 at the selected dose in one of the Sessions I to VI will
again receive TMC558445 at the chosen -intermediate- dose, but now in fasted
condition. Subjects who received placebo will receive placebo again, also in
fasted condition.
Multiple dose:
Part 2 will consist of 4 panels of 9 subjects each. In each panel, 6 subject
will receive TMC558445 and 3 subjects will receive placebo. Please find below
the treatments per panel.
Group 3 Treatment VIII:
- 100 mg twice daily TMC558445 or placebo for 7 consecutive days.
- 300mg TMC310911 on Day 7
Treatment XI:
- 300 or 600mg TMC310911 on Day 1
Group 4 Treatment IX:
- TMC558445 or placebo twice daily for 7 consecutive days.
(dose to be determined)
- 300mg TMC310911 on day 7
Treatment XI:
- 300 or 600 mg TMC310911 on Day 1 (to be determined).
Group 5 Treatment X:
- TMC558445 or placebo once or twice daily for 7 consecutive days
(dose to be determined)
- 300 or 600 mg TMC310911 on Day 7 (to be determined).
Treatment XI:
300 or 600 mg TMC310911 on Day 1 (to be determined).
Group 6 Treatment XII:
- 200 mg TMC558445 or placebo once daily for 7 consecutive days.
- DRV 800mg on Day 7.
Treatment XIII:
- DRV 800mg on Day 1.
.
Study burden and risks
The risks associated with this investigation are linked together with the
possible side effects of the investigational products. The burden on the
volunteer will continue to work with the recording periods, venapunctions and
the introduction of the cannula. All volunteers are closely monitored and
supervised by experienced doctors and studystaff for possible side effects.
The following tests will be performed during this trial: physical examination,
measuring bloodpressure and hart rate, blood- and urine tests, pregnancy test
(women only), drugscreen, alcohol tests, ECGs, restrictions in living habits,
standardized meals during admission.
Al volunteers will be closely monitored by experienced physicians and staff.
Dr. Paul Janssenweg 150
5026 RH Tilburg
Nederland
Dr. Paul Janssenweg 150
5026 RH Tilburg
Nederland
Listed location countries
Age
Inclusion criteria
1) 18-60 years;
2) Nonsmoker;
3) BMI 18.0-30.0;
4) Signed ICF
5) Able to comply with protocol requirements
6) Healthy based on the basis of a medical evaluation.
Exclusion criteria
1) History of clinically significant heart arrhythmias;
2) Female except if they are of non-childbearing potential;
3) History or evidence of alcohol and or drug abuse ;
4) Hepatitis A, B en C;
5) Positive urine drug test;
6) Currently active or underlying gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory or infectious disease;
7) Any history of significant skin disease such as but not limited to rash or eruptions, drug allergies, food allergy, dermatitis, eczema, psoriasis or urticaria
8) History of drug allergy;
9) Use of concomitant medication, except for paracetamol and ibuprofen in the 14 before first trial medication intake;
10) Participation in an investigational drug trial within 60 days prior to the first intake of trial medication;
11) Donation of blood plasma within the 60 days preceding the first intake of trial medication;
12) Lab abnormalities.
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 | EUCTR2008-008133-10-NL |
| CCMO | NL26300.040.09 |