A Study of Ritonavir-Boosted Invirase (Saquinavir) in Treatment-Naïve HIV-1 Infected Patients

HIV Infections Clinical Trial

Official title:

To Determine the Effect of the Modified SQV/r (Saquinavir-boosted by Ritonavir) Regimen (500/100 mg for the 1st Week Followed by 1000/100 mg for the 2nd Week) on the QTc Interval, Pharmacokinetics, and Antiviral Activity in Treatment-naive HIV-1 Infected Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01638650
• Other study ID #: NP25607
• Status: Completed
• Phase: Phase 1
• First received: June 6, 2012
• Last updated: November 1, 2016
• Start date: January 2012
• Est. completion date: June 2012

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This open-label study will evaluate the safety, pharmacokinetics and antiviral activity of a modified Invirase (saquinavir)/ritonavir regimen in treatment-naïve HIV-1 infected patients. Patients will receive Invirase 500 mg plus ritonavir 100 mg twice daily orally for the first week, followed by Invirase 1000 mg plus ritonavir 100 mg twice daily orally for the second week. The study treatment will be given in combination with two Nucleoside Reverse Transcriptase Inhibitors (NRTIs), in accordance with the current clinical HIV treatment guidelines. Anticipated time on study treatment is 14 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients, >/= 18 years of age

• HIV-1 infection

• Currently treatment-naïve and eligible to initiate a ritonavir-boosted Protease Inhibitor based regimen and willing and able to initiate saquinavir/ritonavir therapy for the first 14 days; the saquinavir/ritonavir regimen will be in combination with two Nucleoside Reverse Transcriptase Inhibitors (NRTIs), in accordance with the current clinical HIV treatment guidelines

• Body mass index 18-32 kg/m2, inclusive

• Female patients of childbearing potential and male patients with female partners of childbearing potential must use 2 methods of contraception as defined by protocol during the study and for at least one month after the last dose of study drug

• Non-smoker or patients who have stopped smoking more than three months prior to Day 1 of the study

Exclusion Criteria:

• Coinfection with hepatitis B or C (acute or chronic)

• Anticipated use or need for significant concomitant medical treatment during the study period, other than background antiretroviral therapy

• Participation in a clinical study with an investigational drug or device within 3 months prior to Day 1 of the study

• Pregnant or lactating women

• Any clinically relevant history of substance abuse or addiction including alcohol and/or other drugs of abuse

• Special dietary restrictions that would prohibit consumption of standardized meal (e.g. vegetarian, vegan, gluten-free, lactose-free, kosher)

• Decompensated liver disease

• Congenital or documented acquired QT prolongation

• Electrolyte disturbances, particularly uncorrected hypokalaemia

• Clinically relevant bradycardia

• Clinically relevant heart failure with reduced left-ventricular ejection fraction

• Previous history of symptomatic arrhythmias

• History of clinically significant gastro-intestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological, , hematological, or allergic disease, metabolic disorder, cancer, or cirrhosis

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Nucleoside Reverse Transcriptase Inhibitor (NRTIs)
in accordance with current clinical HIV treatment guidelines
• ritonavir
100 mg bid orally, Days 1-14
• saquinavir [Invirase]
500 mg bid orally Days 1-7, 1000 mg bid orally Days 8-14

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal increase in QTc interval (continuous Holter 12-lead ECG monitoring time points Days 1, 3, 4, 7, 10 and 14)		14 days	Yes
Secondary	Pharmacokinetics: Plasma concentrations		Pre-dose and 2, 4, 6, 8 and 12 hours post-dose, Days 3, 4, 7, 10 and 14	No
Secondary	Pharmacodynamics: Change in HIV-RNA levels		from baseline to Day 14	No
Secondary	Safety: Incidence of adverse events		approximately 6 months	No
Secondary	Change in ECG parameters		from baseline to Day 14	No
Secondary	Correlation between saquinavir plasma concentration and QTc interval changes		approximately 6 months	No