Intracellular boosting of HIV protease inhibitors through inhibition of transport - a novel strategy for potentiating HIV therapy - Intracellular Boosting of HIV Protease Inhibitors

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2008-002627-90-GB

Enrollment

100

Registered

2008-07-25

Start date

2008-09-05

Completion date

Unknown

Last updated

2019-12-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

This study is to evaluate the intracellular boosting effect of furosemide and dipyridamole of the HIV protease inhibitors in HIV positive patients.

Interventions

Trade Name: Furosemide Product Name: Furosemide Pharmaceutical Form: Tablet INN or Proposed INN: FUROSEMIDE CAS Number: 54319

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: •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. •Male or female patients •= 18 years •HIV positive Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: •History of drug sensitivity or drug allergy to lopinavir, ritonavir, furosemide, dipyridamole • 5000 copies •Anaemia (Hb < 10.0 g.dl-1) •Severe coronary artery disease •Unstable angina •Recent myocardial infarction or haemodynamic instability •Severe hypotension (systolic < 100 mm Hg or diastolic < 60 mm Hg) •Hypovolaemia or dehydration •Renal dysfunction (eGFR < 70 ml/min/1.73 m2) •Severe hypokalaemia (K+ < 3.0 mmol.l-1) •Severe hyponatraemia (Na+ < 130 mmol.l-1) •Men with symptomatic urinary outflow obstruction •Any known bleeding disorders •INR < 1.5 •Platelets < 100 109.l-1

Design outcomes

Primary

Measure	Time frame
Secondary Objective: To evaluate the safety of two doses each of dipyridamole and furosemide in HIV positive patients receiving protease inhibitors. To evaluate the correlation between any boosting effect of dipyridamole or furosemide and relative expression of drug transporters in PBMCs. To examine the relationship between transporter genotype and intracellular accumulation of protease inhibitors. To evaluate any change in QTc and PR intervals ; Primary end point(s): The primary endpoint will be a change in cellular accumulation ratio (CAR) of LPV following treatment with dipyridamole and/or furosemide. CAR will be calculated as a ratio of intracellular and plasma AUC of LPV. The secondary endpoints are: •Absolute change in plasma AUC •Absolute change in intracellular AUC •Safety and tolerability of furosemide and dipyridamole •Correlation between drug transporter expression on PBMCs at baseline and i)intracellular drug exposure ii)intracellular boosting effect of furosemide and/or dipyridamole iii)polymorphisms in host genotype of transporter •Absolute QTc interval •Change in QTc interval from baseline ;Main Objective: To evaluate the intracellular boosting effect of dipyridamole and furosemide of the HIV protease inhibitors, in HIV positive patients.	—

Measure

Time frame

Secondary Objective: To evaluate the safety of two doses each of dipyridamole and furosemide in HIV positive patients receiving protease inhibitors. To evaluate the correlation between any boosting effect of dipyridamole or furosemide and relative expression of drug transporters in PBMCs. To examine the relationship between transporter genotype and intracellular accumulation of protease inhibitors. To evaluate any change in QTc and PR intervals ; Primary end point(s): The primary endpoint will be a change in cellular accumulation ratio (CAR) of LPV following treatment with dipyridamole and/or furosemide. CAR will be calculated as a ratio of intracellular and plasma AUC of LPV. The secondary endpoints are: •Absolute change in plasma AUC •Absolute change in intracellular AUC •Safety and tolerability of furosemide and dipyridamole •Correlation between drug transporter expression on PBMCs at baseline and i)intracellular drug exposure ii)intracellular boosting effect of furosemide and/or dipyridamole iii)polymorphisms in host genotype of transporter •Absolute QTc interval •Change in QTc interval from baseline ;Main Objective: To evaluate the intracellular boosting effect of dipyridamole and furosemide of the HIV protease inhibitors, in HIV positive patients.

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Countries

United Kingdom

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026