Pediatric Heterozygous HypercholesterolemiaPhase 1NCT00739999
8-Week PK/PD Atorvastatin Study In Children And Adolescents With Heterozygous Familial Hypercholesterolemia
A Phase 1 study testing Atorvastatin in people with Pediatric Heterozygous Hypercholesterolemia, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 3 sites in 3 countries.
Trial summary
To evaluate pharmacokinetics, pharmacodynamics, safety and tolerability of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Pediatric Heterozygous Hypercholesterolemia
- What is being tested?
- Atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Dec 2008to May 2009
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Genetically confirmed heterozygous familial hypercholesterolemia (HeFH) with LDL greater or equal 4 mmol/L at baseline
Who cannot join
- Evidence or history of clinically significant diseases, homozygous familial hypercholesterolemia (FH)
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
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
To evaluate pharmacokinetics, pharmacodynamics, safety and tolerability of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia
- Being tested
- Atorvastatin
- Keywords
- heterozygous familial hypercholesterolemia (HeFH); atorvastatin; pediatric
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
6-10 years Tanner Stage 1 will be administered 5-mg daily dose of an atorvastatin pediatric tablet formulation. Dose may be doubled if subjects have not attained target LDL (<3.35 mmol/L) after 4-week treatment.
AtorvastatinDrug
10-17 years Tanner Stage 2 will be administered 10-mg daily dose of atorvastatin tablet formulation. Dose may be doubled if subjects have not attained target LDL (<3.35 mmol/L) after 4-week treatment.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | 6-10 years will be administered with atorvastatin tablet formulation with initial doses based on age cohort. Receives: Drug: Atorvastatin |
| 2 | Other | 10-17 years will be administered 10-mg daily dose of atorvastatin tablet formulation. Receives: Drug: Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 2, Week 4, Week 6, Week 8
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.
Measured: Week 2, Week 4, Week 6, Week 8
Secondary outcomes (16)
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.
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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]).
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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.
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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]).
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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.
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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]).
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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.
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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]).
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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.
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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]).
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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.
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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]).
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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]).
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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]).
Measured: Baseline, Week 2, Week 4, Week 6, Week 8
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.
Measured: Baseline, Week 8
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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Measured: Baseline, Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2008 (estimated)
- Study startDec 2008
- Primary completionMay 2009
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pediatric Heterozygous HypercholesterolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00739999
- Sponsor's protocol ID
- A2581172
- Status last verified
- Feb 2021
- First submitted
- 21 Aug 2008
- Last updated
- 15 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00739999
- Acronym / sponsor ID
- A2581172
- Keywords
- heterozygous familial hypercholesterolemia (HeFH); atorvastatin; pediatric
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 22 Aug 2008 (estimated)
- Results
- Posted 20 Aug 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate pharmacokinetics, pharmacodynamics, safety and tolerability of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Other | Drug: Atorvastatin6-10 years will be administered with atorvastatin tablet formulation with initial doses based on age cohort. |
| 2 | Other | Drug: Atorvastatin10-17 years will be administered 10-mg daily dose of atorvastatin tablet formulation. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Genetically confirmed heterozygous familial hypercholesterolemia (HeFH) with LDL greater or equal 4 mmol/L at baseline
Key exclusion criteria (1 listed)
- Evidence or history of clinically significant diseases, homozygous familial hypercholesterolemia (FH)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atorvastatin6-10 years Tanner Stage 1 will be administered 5-mg daily dose of an atorvastatin pediatric tablet formulation. Dose may be doubled if subjects have not attained target LDL (<3.35 mmol/L) after 4-week treatment. | Drug | 1 |
| Atorvastatin10-17 years Tanner Stage 2 will be administered 10-mg daily dose of atorvastatin tablet formulation. Dose may be doubled if subjects have not attained target LDL (<3.35 mmol/L) after 4-week treatment. | Drug | 2 |
Primary outcome
Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Atorvastatin Apparent Clearance (CL/F)
Time frame: Week 2, Week 4, Week 6, Week 8
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.
Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Apparent Volume of Distribution of the Central Compartment (Vc/F)
Time frame: Week 2, Week 4, Week 6, Week 8
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.
16 secondary outcomes
Absolute Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Percent Change From Baseline in Pharmacodynamic Responses of Low-density Lipoprotein Cholesterol (LDL-C)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Absolute Change From Baseline in Total Cholesterol (TC)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Percent Change From Baseline in Total Cholesterol (TC)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Absolute Change From Baseline in Triglycerides (TG)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Percent Change From Baseline in Triglycerides (TG)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Absolute Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Absolute Change From Baseline in Apolipoprotein A-1 (Apo A-1)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Absolute Change From Baseline in Apolipoprotein B (Apo B)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Percent Change From Baseline in Apolipoprotein B (Apo B)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Absolute Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Percent Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C)
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8
Absolute Change From Baseline in Flow-Mediated Dilatation at Week 8
Time frame: Baseline, Week 8
Percent Change From Baseline in Flow-Mediated Dilatation at Week 8
Time frame: Baseline, Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Related trials for Pediatric Heterozygous Hypercholesterolemia
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The ORIGIN-FH Study
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A Study of Enlicitide Decanoate (MK-0616, an Oral PCSK9 Inhibitor) in Children and Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0616-029)
Heterozygous Familial Hypercholesterolemia (HeFH)
RecruitingPhase 3
Long-term Safety and Tolerability of Inclisiran in Participants With HeFH or HoFH Who Have Completed the Pediatric ORION-16, ORION-13, ORION-20, or ORION-19 Studies
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Long-Term Efficacy and Safety of Lerodalcibep in Children and Adolescents With Familial Hypercholesterolemia
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RecruitingPhase 3
Study to Evaluate Efficacy and Safety of Inclisiran in Children With Heterozygous Familial Hypercholesterolemia
Familial Hypercholesterolemia - Heterozygous
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Atorvastatin in people with Pediatric Heterozygous Hypercholesterolemia, run by Pfizer's Upjohn has merged with Mylan to form Viatris Inc. at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada, Greece, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Aug 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Parent-metabolite Population Pharmacokinetic (PK) Model for Atorvastatin and Its Metabolites: Atorvastatin Apparent Clearance (CL/F) (time frame: Week 2, Week 4, Week 6, Week 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2021.