Homozygous Familial HypercholesterolemiaPhase 2NCT01556906
Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor
A Phase 2 study testing Lomitapide in people with Homozygous Familial Hypercholesterolemia, run by Aegerion Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
The primary objective of this study is to evaluate the safety and tolerability of 4 doses of lomitapide (AEGR-733; BMS-201038) given as an initial low dose and then escalated through an additional 3 dose levels over a 16-week period. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Homozygous Familial Hypercholesterolemia
- What is being tested?
- Lomitapide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2003to Feb 2004
- Phase
- Phase 2
- 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 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Males and females ≥13 years of age
- Clinical diagnosis of HoFH AND one of the following (a, b, or c):
- Documented functional mutation in both LDL receptor alleles, OR
- Skin fibroblast LDL receptor activity <20% of normal, OR
- TC >500 mg/dL AND triglycerides < 300 mg/dL AND both parents with documented TC >250 mg/dL
- Body weight ≥40 kg
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- Negative screening pregnancy test if female of child-bearing potential
- Subjects must be willing and able to comply with all study-related procedures
- Subjects must be willing and able to go off all lipid-lowering medications, dietary supplements (psyllium preparations) and LDL apheresis within 4 weeks prior to the Baseline visit until the end of the study.
Who cannot join
- Uncontrolled hypertension defined as: systolic blood pressure >180 mmHg, diastolic blood pressure >95 mmHg
- History of chronic renal insufficiency (serum creatinine >2.5 mg/dL)
- History of liver disease or abnormal LFTs at screening (>3x upper limit of normal [ULN])
- Any major surgical procedure occurring < 3 months prior to the screening visit
- Cardiac insufficiency defined by the New York Heart Association classification as functional Class III or Class IV
- History of a non-skin malignancy within the previous 5 years
Show all 9Show fewer
- History of alcohol or drug abuse
- Participation in an investigational drug study within 6 weeks prior to the screening visit
- Serious or unstable medical or psychological conditions that, in the opinion of the Investigator, would compromise the patient's safety or successful participation in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase II Open Label, Dose-Escalation Study to Determine the Safety, Tolerability and Efficacy of Microsomal Triglyceride Transfer Protein (MTP) Inhibitor BMS-201038 in Patients With Homozygous Familial Hypercholeterolemia
The primary objective of this study is to evaluate the safety and tolerability of 4 doses of lomitapide (AEGR-733; BMS-201038) given as an initial low dose and then escalated through an additional 3 dose levels over a 16-week period.
The secondary objectives of this study included the evaluation of the pharmacodynamics of lomitapide based on:
- Percent change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides, and very low density lipoprotein cholesterol (VLDL-C) concentrations at the end of each 4-week dosing period compared to the Baseline value of each parameter at the end of the previous dose phase(s).
- Changes in other plasma lipoproteins: apolipoproteins (apo B, apo AI, apo AII, apo CIII, apo E) and lipoprotein a [Lp(a)].
Read the detailed description
This is a single center, open-label, Phase 2 clinical trial designed to evaluate the safety, tolerability, and pharmacodynamics of lomitapide in the treatment of patients with homozygous familial hypercholesterolemia (HoFH).
Patients are required to stop all lipid-lowering therapies, including apheresis, within 4 weeks prior to the Baseline visit and throughout the study. Patients are placed on a rigorous low-fat diet (<10% of energy from total dietary fat) at the Screening assessment; dietary counseling by a registered dietitian will be initiated at Screening and will continue at each subsequent study visit.
Patients initially receive 0.03 mg/kg of lomitapide orally every day for 4 weeks. Intra-patient dose escalation to 0.1 mg/kg, 0.3 mg/kg/day and 1.0 mg/kg/day occur every 4 weeks if specific protocol-defined stopping rules related to Grade 3 or 4 toxicities or serious adverse events (SAEs) do not apply.
The study includes 15 study visits over 22 weeks: a Screening visit (Visit 1) conducted within 2 weeks prior to dosing, a Baseline visit (Visit 2) conducted on Day 1 prior to the first dose, 12 visits conducted during the treatment period (Visits 3 through 14), and a Follow-up visit (Visit 15) conducted approximately 4 weeks after the last dose of lomitapide.
Screening and Baseline procedures include medical and medication history, physical examination, vital signs, 12-lead electrocardiogram (ECG), pulmonary function tests (PFTs), safety laboratory tests, fat soluble vitamin levels and a fatty acid profile. Nuclear magnetic resonance spectroscopy (NMRS) of the liver will be conducted at Baseline, at the end of each dosing period, and at the follow up visit to assess hepatic fat content. Baseline efficacy assessment includes a fasting lipid profile (TC, LDL-C [directly measured], VLDL-C, high density lipoprotein-cholesterol [HDL-C], triglycerides, and apolipoproteins [apo B, apo AI, apo AII, apo CIII, apo E] and Lp(a)).
Safety and lipid profile assessments are repeated during the treatment period and at the Follow-up visit conducted 28 days after the last dose of lomitapide.
- Conditions
- Homozygous Familial Hypercholesterolemia
- Being tested
- Lomitapide
- Medical subject headings
- Homozygous Familial Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LomitapideDrug
Also called AEGR-733, BMS-201038
Oral administration with escalating doses administered once daily
| Study group | Role | What they receive |
|---|---|---|
| Lomitapide | Experimental | This is an open label trial where all patients receive lomitapide (AEGR733/BMS-201038)at escalating doses Receives: Drug: Lomitapide |
What is being measured
The primary outcome is the main question the study is designed to answer.
LDL-C
Percent change in LDL-C compared to Baseline.
Measured: Up to 16 weeks of treatment comapred to Baseline
Secondary outcomes (14)
Absolute Change From Baseline in Alanine Aminotransferase (ALT)
Absolute change from Baseline in ALT
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Aspartate Aminotransferase (AST)
Absolute change from Baseline in AST
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Total Bilirubin
Absolute change from Baseline in total bilirubin
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Hepatic Fat Percent
Absolute change from Baseline in hepatic fat percent
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Forced Expiratory Volume During 1 Second (FEV1)
Absolute change from Baseline in FEV1
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Carbon Monoxide Lung Diffusing Capacity (DLCO)(a Pulmonary Function Test)
Absolute change from Baseline in DLCO
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Vitamin A
Absolute change from Baseline in vitamin A
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Vitamin E
Absolute change from Baseline in vitamin E
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Vitamin D
Absolute Change From Baseline in Vitamin D
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Ratio of Vitamin E to Total Lipids
Absolute Change From Baseline in ratio of vitamin E to total lipids
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Alpha Linoleic Acid (ALA)
Absolute Change From Baseline in ALA
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Eicosapentaenoic Acid (EPA)
Absolute Change From Baseline in EPA
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Docosahexaenoic Acid (DHA)
Absolute Change From Baseline in DHA
Measured: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Linoleic Acid (LA)
Absolute Change From Baseline in LA
Measured: Baseline and 16 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2012 (estimated)
- Study startJun 2003
- Primary completionFeb 2004
- Study completionFeb 2004
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Homozygous Familial 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aegerion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Pennsylvania, Doris Duke Charitable Foundation
- Responsible party
- Sponsor
- Investigators
- Dan J Rader, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01556906
- Sponsor's protocol ID
- UP1001
- Status last verified
- Apr 2013
- First submitted
- 7 Mar 2012
- Last updated
- 10 Apr 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007 Jan 11;356(2):148-56. doi: 10.1056/NEJMoa061189.
PubMed 17215532
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open Label, Dose-Escalation Study to Determine the Safety, Tolerability and Efficacy of Microsomal Triglyceride Transfer Protein (MTP) Inhibitor BMS-201038 in Patients With Homozygous Familial Hypercholeterolemia
- ClinicalTrials.gov ID
- NCT01556906
- Acronym / sponsor ID
- UP1001
- Conditions
- Homozygous Familial Hypercholesterolemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Aegerion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- University of Pennsylvania, Doris Duke Charitable Foundation
- Study start
- Jun 2003
- Primary completion
- Feb 2004 (actual)
- Study completion
- Feb 2004 (actual)
- First posted
- 19 Mar 2012 (estimated)
- Results
- Posted 22 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the safety and tolerability of 4 doses of lomitapide (AEGR-733; BMS-201038) given as an initial low dose and then escalated through an additional 3 dose levels over a 16-week period.
The secondary objectives of this study included the evaluation of the pharmacodynamics of lomitapide based on:
- Percent change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides, and very low density lipoprotein cholesterol (VLDL-C) concentrations at the end of each 4-week dosing period compared to the Baseline value of each parameter at the end of the previous dose phase(s).
- Changes in other plasma lipoproteins: apolipoproteins (apo B, apo AI, apo AII, apo CIII, apo E) and lipoprotein a [Lp(a)].
Detailed description
This is a single center, open-label, Phase 2 clinical trial designed to evaluate the safety, tolerability, and pharmacodynamics of lomitapide in the treatment of patients with homozygous familial hypercholesterolemia (HoFH).
Patients are required to stop all lipid-lowering therapies, including apheresis, within 4 weeks prior to the Baseline visit and throughout the study. Patients are placed on a rigorous low-fat diet (<10% of energy from total dietary fat) at the Screening assessment; dietary counseling by a registered dietitian will be initiated at Screening and will continue at each subsequent study visit.
Patients initially receive 0.03 mg/kg of lomitapide orally every day for 4 weeks. Intra-patient dose escalation to 0.1 mg/kg, 0.3 mg/kg/day and 1.0 mg/kg/day occur every 4 weeks if specific protocol-defined stopping rules related to Grade 3 or 4 toxicities or serious adverse events (SAEs) do not apply.
The study includes 15 study visits over 22 weeks: a Screening visit (Visit 1) conducted within 2 weeks prior to dosing, a Baseline visit (Visit 2) conducted on Day 1 prior to the first dose, 12 visits conducted during the treatment period (Visits 3 through 14), and a Follow-up visit (Visit 15) conducted approximately 4 weeks after the last dose of lomitapide.
Screening and Baseline procedures include medical and medication history, physical examination, vital signs, 12-lead electrocardiogram (ECG), pulmonary function tests (PFTs), safety laboratory tests, fat soluble vitamin levels and a fatty acid profile. Nuclear magnetic resonance spectroscopy (NMRS) of the liver will be conducted at Baseline, at the end of each dosing period, and at the follow up visit to assess hepatic fat content. Baseline efficacy assessment includes a fasting lipid profile (TC, LDL-C [directly measured], VLDL-C, high density lipoprotein-cholesterol [HDL-C], triglycerides, and apolipoproteins [apo B, apo AI, apo AII, apo CIII, apo E] and Lp(a)).
Safety and lipid profile assessments are repeated during the treatment period and at the Follow-up visit conducted 28 days after the last dose of lomitapide.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lomitapide | Experimental | Drug: LomitapideThis is an open label trial where all patients receive lomitapide (AEGR733/BMS-201038)at escalating doses |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Males and females ≥13 years of age
- Clinical diagnosis of HoFH AND one of the following (a, b, or c):
- Body weight ≥40 kg
- Negative screening pregnancy test if female of child-bearing potential
- Subjects must be willing and able to comply with all study-related procedures
Key exclusion criteria (9 listed)
- Uncontrolled hypertension defined as: systolic blood pressure >180 mmHg, diastolic blood pressure >95 mmHg
- History of chronic renal insufficiency (serum creatinine >2.5 mg/dL)
- History of liver disease or abnormal LFTs at screening (>3x upper limit of normal [ULN])
- Any major surgical procedure occurring < 3 months prior to the screening visit
- Cardiac insufficiency defined by the New York Heart Association classification as functional Class III or Class IV
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 |
|---|---|---|
| LomitapideAlso: AEGR-733, BMS-201038Oral administration with escalating doses administered once daily | Drug | Lomitapide |
Primary outcome
LDL-C
Time frame: Up to 16 weeks of treatment comapred to Baseline
Percent change in LDL-C compared to Baseline.
14 secondary outcomes
Absolute Change From Baseline in Alanine Aminotransferase (ALT)
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Aspartate Aminotransferase (AST)
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Total Bilirubin
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Hepatic Fat Percent
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Forced Expiratory Volume During 1 Second (FEV1)
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Carbon Monoxide Lung Diffusing Capacity (DLCO)(a Pulmonary Function Test)
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Vitamin A
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Vitamin E
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Vitamin D
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Ratio of Vitamin E to Total Lipids
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Alpha Linoleic Acid (ALA)
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Eicosapentaenoic Acid (EPA)
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Docosahexaenoic Acid (DHA)
Time frame: Baseline and 16 weeks of treatment
Absolute Change From Baseline in Linoleic Acid (LA)
Time frame: Baseline and 16 weeks of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 17215532Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007 Jan 11;356(2):148-56. doi: 10.1056/NEJMoa061189.
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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.
Dan J Rader, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lomitapide in people with Homozygous Familial Hypercholesterolemia, run by Aegerion Pharmaceuticals, Inc. at 1 site in United States.
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 9 inclusion and 9 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 10 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 22 Feb 2013). 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?
LDL-C (time frame: Up to 16 weeks of treatment comapred to Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01556906, which also lists 1 linked publication.
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 10 Apr 2013.