PK of Efavirenz & Lopinavir Nano-formulations in Healthy Volunteers

NCT ID: NCT02631473

Last Updated: 2016-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE1

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Brief Summary

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This study is an open-label, prospective pharmacokinetic study investigating two antiretroviral agents in parallel and employing an adaptive design with two stages, whereby the results obtained in the primary stage inform the doses selected for investigation in the secondary stage

Detailed Description

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The objectives of this study are:

Primary

* To investigate the pharmacokinetics of a new pharmaceutical formulation of efavirenz (NANO-efavirenz) in HIV negative healthy volunteers after single dose and a steady-state.
* To investigate the pharmacokinetics of a new pharmaceutical formulation of lopinavir (NANO-lopinavir) in HIV negative healthy volunteers

Secondary

* To investigate the safety and tolerability of NANO-efavirenz and NANO-lopinavir in HIV negative healthy volunteers
* To assess the bioequivalence of a selected single-dose of NANO-efavirenz to a single dose 600mg of efavirenz as Sustiva®
* To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure

Conditions

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HIV

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1st Stage-Group A

1. Day 1: 50 mg NANO-efavirenz single dose
2. Days 4-21: 50 mg NANO-efavirenz OD (once daily)

Group Type ACTIVE_COMPARATOR

50mg NANO-efavirenz

Intervention Type DRUG

OD

1st Stage-Group B

1. Days 1-7: 400mg NANO-lopinavir BID (twice daily)
2. Days 8-21: Wash-out period
3. Days: 22-28: 200mg NANO-lopinavir BID plus 100mg Ritonavir (Norvir) BID

Group Type ACTIVE_COMPARATOR

400mg NANO-Lopinavir

Intervention Type DRUG

BID

200mg NANO-Lopinavir

Intervention Type DRUG

BID

100mg Ritonavir

Intervention Type DRUG

BID

2nd Stage-Group A-Group 1-Dose level 1

1. 21 Days: 300mg NANO-efavirenz OD
2. 4 weeks: Wash-out period
3. 21 days: 600mg Sustiva OD

Group Type ACTIVE_COMPARATOR

300mg NANO-Efavirenz

Intervention Type DRUG

OD

600mg Sustiva

Intervention Type DRUG

OD

2nd Stage-Group A-Group 2-Dose level 2

1. 21 Days: 200mg NANO-efavirenz OD
2. 4 weeks: Wash-out period
3. 21 days: 400mg Sustiva OD

Group Type ACTIVE_COMPARATOR

200mg NANO-Efavirenz

Intervention Type DRUG

OD

400mg Sustiva

Intervention Type DRUG

2nd Stage-Group B-Arm 1

1. 7 days: Kaletra® (lopinavir400mg/ritonavir100mg) BD
2. 2 weeks: Wash-out period
3. 7 days: NANO-lopinavir (200mg +/- ritonavir®)

Group Type ACTIVE_COMPARATOR

Kaletra® (lopinavir 400mg/ritonavir 100mg)

Intervention Type DRUG

BID

+/- 200mg NANO-Lopinavir

Intervention Type DRUG

BID

+/- 200mg ritonavir NORVIR

Intervention Type DRUG

BID

2nd Stage-Group B-Arm 2

1. 7 days: NANO-lopinavir (200mg +/- ritonavir Norvir)
2. 2 weeks: Wash-out period
3. 7 days: Kaletra® (lopinavir400mg/ritonavir100mg) BD

Group Type ACTIVE_COMPARATOR

Kaletra® (lopinavir 400mg/ritonavir 100mg)

Intervention Type DRUG

BID

+/- 200mg NANO-Lopinavir

Intervention Type DRUG

BID

+/- 200mg ritonavir NORVIR

Intervention Type DRUG

BID

Interventions

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50mg NANO-efavirenz

OD

Intervention Type DRUG

400mg NANO-Lopinavir

BID

Intervention Type DRUG

200mg NANO-Lopinavir

BID

Intervention Type DRUG

100mg Ritonavir

BID

Intervention Type DRUG

300mg NANO-Efavirenz

OD

Intervention Type DRUG

600mg Sustiva

OD

Intervention Type DRUG

200mg NANO-Efavirenz

OD

Intervention Type DRUG

Kaletra® (lopinavir 400mg/ritonavir 100mg)

BID

Intervention Type DRUG

+/- 200mg NANO-Lopinavir

BID

Intervention Type DRUG

+/- 200mg ritonavir NORVIR

BID

Intervention Type DRUG

400mg Sustiva

Intervention Type DRUG

Other Intervention Names

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Efavirenz Norvir Efavirenz Lopinavir/Ritonavir Ritonavir Efavirenz

Eligibility Criteria

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Inclusion Criteria

1. The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
2. Male or non-pregnant, non-lactating females
3. Between 18 to 65 years, inclusive
4. Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive
5. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 12 weeks after the study

A female may be eligible to enter and participate in the study if she:
1. is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
2. is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:

* Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications;
* Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
* Any intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year (not all IUDs meet this criterion, see protocol appendix 7 for an example listing of approved IUDs);
* Condom and depot medroxyprogesterone acetate ( DMPA) injections
* Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject;
* Any other method with published data showing that the expected failure rate is \<1% per year.
* Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of IP.
6. Willing to consent to their personal details being entered onto the TOPS database
7. Willing to provide proof of identity by photographic ID at screen and any subsequent visit
8. Registered with a GP in the UK

Exclusion Criteria

1. Any significant acute or chronic medical illness including hypertension (BP persistently \>140/90 mmHg) or hypotension (BP persistently \<90/60 mmHg)
2. Prolongation of ECG intervals: PR \> 200 msec or QTcF \> 450 msec.
3. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations.
4. Liver transaminase (ALT or AST \> 1.25 x the upper limit of the normal range)
5. Significant psychiatric history (including severe depression) or history of seizures.
6. Positive blood screen for either hepatitis B surface antigen or hepatitis C antibody
7. Positive blood screen for HIV-1 and/or 2 antibodies
8. Current or recent (within 3 months) gastrointestinal disease
9. Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder adherence to treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
10. Known cardiac disease history of any family history of sudden cardiac death.
11. Exposure to any investigational drug or placebo within 3 months of first dose of study drug
12. Use of any other drugs (unless approved by the Investigator), including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.
13. Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least 12 weeks after the end of the treatment period
14. Previous allergy to any of the constituents of the pharmaceuticals administered in this trial
15. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Liverpool

OTHER

Sponsor Role collaborator

St Stephens Aids Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marta Boffito

Role: PRINCIPAL_INVESTIGATOR

Chelsea & Westminster Hospital

Steve Rannard

Role: STUDY_DIRECTOR

University of Liverpool

Locations

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St Stephen's Centre

London, London, United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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SSAT 055

Identifier Type: -

Identifier Source: org_study_id