Pediatric Heterozygous Hypercholesterolemia Clinical Trial
Official title:
A 8-Week, Open-Label, Phase 1 Study To Evaluate Pharmacokinetics, Pharmacodynamics, Safety And Tolerability Of Atorvastatin In Children And Adolescents With Heterozygous Familial Hypercholesterolemia
| NCT number | NCT00739999 |
| Other study ID # | A2581172 |
| Secondary ID | |
| Status | Completed |
| Phase | Phase 1 |
| First received | |
| Last updated | |
| Start date | December 2008 |
| Est. completion date | May 2009 |
| Verified date | February 2021 |
| Source | Pfizer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
To evaluate pharmacokinetics, pharmacodynamics, safety and tolerability of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia
| Status | Completed |
| Enrollment | 39 |
| Est. completion date | May 2009 |
| Est. primary completion date | May 2009 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 6 Years to 17 Years |
| Eligibility | Inclusion Criteria: - Genetically confirmed heterozygous familial hypercholesterolemia (HeFH) with LDL greater or equal 4 mmol/L at baseline Exclusion Criteria: - Evidence or history of clinically significant diseases, homozygous familial hypercholesterolemia (FH) |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Pfizer Investigational Site | Quebec | |
| Greece | Pfizer Investigational Site | Athens | |
| Norway | Pfizer Investigational Site | Oslo |
| Lead Sponsor | Collaborator |
|---|---|
| Pfizer's Upjohn has merged with Mylan to form Viatris Inc. |
Canada, Greece, Norway,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Atorvastatin Apparent Clearance (CL/F) | Parent-metabolite population PK model built using sparse blood samples from both Tanner Stage 1 and Tanner Stage 2+. Blood sampling times: Weeks 2 and 6: single sample between 4 and 12 hours postdose; Weeks 4 and 8: predose, 1 hour, and 2 hours postdose. Plasma samples were analyzed for atorvastatin and active hydroxyacid metabolite (o-hydroxyatorvastatin) concentrations using a validated, sensitive, and specific high-performance liquid chromatography tandem mass spectrometric method. Data presented are the result of the model used. | Week 2, Week 4, Week 6, Week 8 | |
| Primary | Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Apparent Volume of Distribution of the Central Compartment (Vc/F) | Parent-metabolite population PK model built using sparse blood samples from Tanner Stages 1 and 2+. Sampling times: Weeks 2 + 6: single sample between 4 -12 hours postdose; Weeks 4 + 8: predose, 1 + 2 hours postdose. Plasma samples analyzed for atorvastatin and active hydroxyacid metabolite (o-hydroxyatorvastatin) concentrations using validated, sensitive, specific high-performance liquid chromatography tandem mass spectrometric method. Vc/F value based on 70 kg body weight. Parameter estimation uncertainty (95% CI) by non-parametric bootstrap analysis. Data presented are result of model used. | Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Absolute Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C) | Low-density lipoprotein cholesterol (LDL-C) measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value. | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Percent Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C) | Low-density Lipoprotein Cholesterol (LDL-C): percent (%) change from baseline by treatment over time = [LDL-C at observation minus LDL-C at Week 0] divided by LDL-C at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Absolute Change From Baseline in Total Cholesterol (TC) | Total Cholesterol measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value. | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Percent Change From Baseline in Total Cholesterol (TC) | Total cholesterol (TC): percent (%) change from baseline by treatment over time = [TC at observation minus TC at Week 0] divided by TC at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Absolute Change From Baseline in Triglycerides (TG) | Change from baseline in triglycerides measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value. | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Percent Change From Baseline in Triglycerides (TG) | Triglycerides (TG): percent (%) change from baseline by treatment over time = [TG at observation minus TG at Week 0] divided by TG at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Absolute Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) | Change from baseline in high-density lipoprotein cholesterol measured in millimoles per liter (mmol/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value. | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) | High-density lipoprotein cholesterol (HDL-C): percent (%) change by treatment over time = [HDL-C at observation minus HDL-C at Week 0] divided by HDL-C at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1) | Change from baseline in Apolipoprotein A-1 measured in grams per liter (g/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value. | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) | Apolipoprotein A-1 (Apo A-1): percent (%) change from baseline by treatment over time = [Apo A-1 at observation minus Apo A-1 at Week 0] divided by Apo A-1 at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Absolute Change From Baseline in Apolipoprotein B (Apo B) | Change from baseline in Apolipoprotein B measured in grams per liter (g/L); assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). Change from baseline = value at observation minus baseline value. | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Percent Change From Baseline in Apolipoprotein B (Apo B) | Apolipoprotein B (Apo B): percent (%) change from baseline by treatment over time = [Apo B at observation minus Apo B at Week 0] divided by Apo B at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Absolute Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) | Change from baseline in very low-density lipoprotein-cholesterol (VLDL-C) measured in millimoles per liter (mmol/L). Change from baseline = value at observation minus baseline value. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Percent Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) | Very low-density lipoprotein-cholesterol (VLDL-C): percent (%) change from baseline by treatment over time = [VLDL-C at observation minus VLDL-C at Week 0] divided by VLDL-C at Week 0 * 100. Assessments were performed in the fasting state (minimum 10-hour fast [optional at Weeks 2 and 6]). | Baseline, Week 2, Week 4, Week 6, Week 8 | |
| Secondary | Absolute Change From Baseline in Flow-Mediated Dilatation at Week 8 | Brachial artery flow-mediated dilatation (FMD) = (max minus baseline diameter divided by baseline diameter) x 100%. Standardized image acquisition: brachial artery images recorded for one minute at rest, blood pressure cuff inflated to 250 mm Hg for 5 minutes with brachial artery imaged continuously throughout cuff inflation, cuff released to produce reactive hyperaemia and the brachial artery imaged continuously for 3 minutes after release. Total duration of measurement approximately 25 minutes. Change from baseline = value at observation minus baseline value. | Baseline, Week 8 | |
| Secondary | Percent Change From Baseline in Flow-Mediated Dilatation at Week 8 | Brachial Flow-Mediated Dilatation (FMD) = (max minus baseline diameter divided by baseline diameter) x 100%.
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Baseline, Week 8 |