Pharmacokinetic (PK) Study of Single-dose Rosuvastatin and Tipranavir/Ritonavir in Healthy Subjects

NCT00344123 | Completed Phase 1 DMC

• 1 other identifier: NA_00003633
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Tipranavir (TPV) plus ritonavir (RTV) is indicated for use as part of an antiretroviral treatment regimen for resistant HIV-1 infection in adult patients. Since significant cholesterol and triglyceride elevations are commonly reported during TPV/RTV treatment, effective treatment strategies are critical to prevent long-term cardiovascular events. Rosuvastatin, a potent 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitor, is unlikely to interact with TPV/RTV since it is not extensively metabolized, however, a formal drug interaction study is needed before this combination can be recommended. This study will examine the pharmacokinetic interactions between tipranavir/ritonavir (TPV/RTV \[TPV/r\] 500 mg/200 mg twice daily \[B.I.D\]) and single dose rosuvastatin when the two are co-administered to healthy adult volunteers. The investigators hypothesize that if tipranavir 500 mg is co-administered with low-dose ritonavir 200 mg and rosuvastatin (10 mg) no significant clinical interaction will occur.

Conditions

HIV Infections

Keywords

HIV

Outcome Measures

Primary Outcomes (1)

• To compare single dose rosuvastatin Area Under the Curve during 24 hours (AUC0-24h) and Cmax with single dose rosuvastatin AUC0-24h and Cmax when co-administered with TPV/r 500 mg/200 mg twice daily at steady state

  24 hours

Secondary Outcomes (1)

• To evaluate the short term safety and tolerance of TPV/r (500 mg/200 mg B.I.D) combined with single dose rosuvastatin (10 mg)

  48 hours

Study Arms (1)

Tipranavir/ritonavir

OTHER

On Day 1, subjects will receive a single 10 mg dose of rosuvastatin. Beginning on Day 3, subjects will receive a combination of TPV 500mg/RTV 200 mg twice daily for 11 days (Days 3-13). On Day 12, subjects will receive a single 10 mg dose of rosuvastatin co-administered with TPV/r.

Drug: Tipranavir/Ritonavir; Drug: Rosuvastatin

Interventions

Tipranavir/Ritonavir DRUG

On Day 1, subjects will receive a single 10 mg dose of rosuvastatin. Beginning on Day 3, subjects will receive a combination of TPV 500mg/RTV 200 mg twice daily for 11 days (Days 3-13). On Day 12, subjects will receive a single 10 mg dose of rosuvastatin co-administered with TPV/r.

Also known as: Aptivus

Tipranavir/ritonavir

Rosuvastatin DRUG

On Day 1, subjects will receive a single 10 mg dose of rosuvastatin. Beginning on Day 3, subjects will receive a combination of TPV 500mg/RTV 200 mg twice daily for 11 days (Days 3-13). On Day 12, subjects will receive a single 10 mg dose of rosuvastatin co-administered with TPV/r..

Also known as: Crestor

Tipranavir/ritonavir

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a body mass index (BMI) of 18 to 30 kg/m2, inclusive (BMI = weight (kg)/\[height (m)\]2) and weigh at least 50 kg.
• Males or females, ages \> 18 to \< 65 years.
• Women of childbearing potential (WOCBP) must not be nursing or pregnant. All women of childbearing potential (have not reached menopause nor undergone hysterectomy, bilateral oophorectomy, or tubal ligation) must have a negative serum human chorionic gonadotropin (HCG) test performed at screening (within 24 hours before the start of study day 1). Female subjects who are not of reproductive potential (have reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation) or whose male partner has undergone successful vasectomy with resultant azoospermia or has azoospermia for any other reason, are eligible without requiring the use of contraception. Documentation of menopause, sterilization (hysterectomy, oophorectomy, tubal ligation, or vasectomy) and azoospermia by patient-reported history is acceptable. Both male and female study volunteers of reproductive potential must agree not to participate in a conception process (i.e., active attempt to become pregnant or to impregnate via sperm donation or in vitro fertilization), and, if participating in sexual activity that could lead to pregnancy, the female study volunteer/male partner must use a form of contraception as specified below while receiving protocol-specified medication(s) and for one month after stopping the medication(s). Male study volunteers will be required to use a barrier method for at least 3 months after completion of the study.
• Condoms (male or female) with or without a spermicidal agent
• Diaphragm or cervical cap with spermicide

You may not qualify if:

• History or current evidence of any significant acute or chronic medical illness that, within the investigator's discretion, would interfere with the conduct or interpretation of the study.
• History of acute or chronic pancreatitis.
• History of diabetes mellitus, hypertriglyceridemia, or chronic renal insufficiency.
• Proven or suspected acute hepatitis at the time of study entry.
• Current or recent (within 3 months) gastrointestinal disease which would interfere with the conduct or interpretation of the study.
• Any major surgery within 4 weeks of enrollment. Any gastrointestinal surgery that could impact upon the absorption of study drug.
• Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of enrollment.
• Inability to tolerate oral medication.
• Inability to tolerate venipuncture and/or absence of secure venous access.
• Known or suspected HIV infection or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Known active drug or alcohol abuse which, in the opinion of the investigator, makes study participation to completion unlikely.
• Any other sound medical, psychiatric, and/or social reason, as determined by the investigator.
• Subjects with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin above the upper limit of normal.
• Hemoglobin \< 9.5 g/dL, and platelet count \< 100,000/mm3.
• Subjects with creatine phosphokinase (CPK) elevation greater than 3 times the upper limit of normal.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

tipranavir; Ritonavir; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Pyrimidines

Study Officials

• Paul Pham, PharmD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2006
• First Posted: June 26, 2006
• Study Start: February 1, 2007
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: February 4, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)