View source for A Multiple Ascending Dose Study of CSL112 in Healthy Volunteers

__NOTOC__
{{High density lipoprotein}}

{{CMG}}; {{AE}} {{Rim}}

==Official Title==
An adaptive, phase I, randomized, placebo-controlled, sponsor-unblinded, multiple ascending dose study to investigate the safety, tolerability and pharmacokinetics of intravenous CSL112 in healthy volunteers

==Objectives==
*To measure the biomarkers of cholesterol movement following a single and multiple infusions of CSL-112 in healthy subjects.<ref name="circ.ahajournals.org">{{Cite web  | last =  | first =  | title = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | url = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | publisher =  | date =  | accessdate = 16 September 2013 }}</ref>

*To evaluate role of CSL-112 in decreasing cholesterol-loaded plaques that contribute to cardiovascular disease.<ref name="circ.ahajournals.org">{{Cite web  | last =  | first =  | title = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | url = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | publisher =  | date =  | accessdate = 16 September 2013 }}</ref>

==Sponsor==
CSL Limited

==Timeline==
{| class="wikitable" border="1" style="background:WhiteSmoke" width="40%"
|-
| Colspan="2" style="background:Gainsboro" align="center"|'''Timeline'''
|-
| Style="width:30%"| '''Start Date'''||Style="width:70%"| January 2011
|-
| '''End Date'''||June 2011
|-
| '''Status'''||Completed
|-
|}
<span style="font-size:85%">The previous information was derived from ClinicalTrials.gov on 09/19/2013 using the identification number NCT01281774.</span>

==Study Description==

{| class="wikitable" border="1" style="background:WhiteSmoke" width="40%"
|-
| Colspan="2" style="background:Gainsboro" align="center"|'''Study Description'''
|-
| Style="width:30%"|'''Study Type'''|| Style="width:70%"|Interventional
|-
| '''Study Phase''' ||Phase 1
|-
| Colspan="2" style="background:Gainsboro" align="center"|'''Study Design'''
|-
| '''Allocation'''||Randomized
|-
| '''Endpoint'''||Safety study
|-
| '''Interventional Model'''||Parallel assignment
|-
| '''Masking'''||Double blind
|-
| Colspan="2" style="background:Gainsboro" align="center"|'''Study Details'''
|-
| '''Primary Purpose'''||Treatment
|-
| '''Condition'''||Healthy
|-
| '''Intervention'''||Biological: CSL112 (reconstituted high density lipoprotein)<br>Biological: Placebo (normal saline)
|-
| '''Study Arms'''||Multiple ascending intravenous doses of CSL112<br>Placebo
|-
| '''Population Size'''||36
|-
|}

<span style="font-size:85%">The previous information was derived from ClinicalTrials.gov on 09/19/2013 using the identification number NCT01281774.</span>

==Eligibility Criteria==
===Inclusion Criteria===
*Healthy individual
*Age: 18-55 year old
*Weight ≥ 5 kg
*BMI between 18-42 kg/m2

===Exclusion Criteria===
*Clinically significant medical condition or disease
*Abnormal lab test result
*History of alcohol or other substance abuse

==Outcomes==
===Primary Outcomes===
Safety and tolerability defined as rate of clinically-associated [[adverse events]] that occur within 14 days of CSL112 infusion.<ref name="circ.ahajournals.org">{{Cite web  | last =  | first =  | title = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | url = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | publisher =  | date =  | accessdate = 16 September 2013 }}</ref>
===Secondary Outcomes===
Evaluation of [[lipoprotein]] [[pharmacokinetics]] during a time frame of 10 days following CSL112 infusion and measurement of plasma levels of [[lipoprotein]].<ref name="circ.ahajournals.org">{{Cite web  | last =  | first =  | title = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | url = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | publisher =  | date =  | accessdate = 16 September 2013 }}</ref>
==Publications==
===Results===
* Infusions of CSL-112 caused immediate and profound elevation in all the biomarkers of cholesterol transport, including preBeta1-HDL and global cholesterol efflux as measured by activity of ATP-binding cassette transporter (ABCA1) cells.<ref name="circ.ahajournals.org">{{Cite web  | last =  | first =  | title = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | url = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | publisher =  | date =  | accessdate = 16 September 2013 }}</ref>

* Serum [[preBeta1-HDL]] elevation was up to 20-fold.<ref name="circ.ahajournals.org">{{Cite web  | last =  | first =  | title = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | url = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | publisher =  | date =  | accessdate = 16 September 2013 }}</ref>

*The infusion of CSL112 caused a dose-dependent increase of all biomarkers.  Levels were consistent in magnitude and time course following the first and last infusions.<ref name="circ.ahajournals.org">{{Cite web  | last =  | first =  | title = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | url = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | publisher =  | date =  | accessdate = 16 September 2013 }}</ref>

* Serum [[preBeta1-HDL]] and cholesterol efflux capacity peaked after infusion and returned to baseline at 24 hour while there was a 72 hour sustained response for serum [[HDL]] following its peak at 24-48 hours after infusion.<ref name="circ.ahajournals.org">{{Cite web  | last =  | first =  | title = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | url = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | publisher =  | date =  | accessdate = 16 September 2013 }}</ref>

* Multiple infusions of CSL112 cause a greater efflux of cholesterol from tissues to HDL when compared with a single infusion.<ref name="circ.ahajournals.org">{{Cite web  | last =  | first =  | title = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | url = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | publisher =  | date =  | accessdate = 16 September 2013 }}</ref>

* There were no observed changes in the baseline of other lipoproteins.<ref name="circ.ahajournals.org">{{Cite web  | last =  | first =  | title = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | url = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | publisher =  | date =  | accessdate = 16 September 2013 }}</ref>

===Conclusion===
Single and multiple infusions of CSL-112 in healthy subjects rapidly initiates the reverse [[cholesterol transport]], and this is beneficial in rapidly lowering the risk of recurrent [[cardiovascular events]] following [[acute coronary syndromes]].<ref name="circ.ahajournals.org">{{Cite web  | last =  | first =  | title = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | url = http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A11851 | publisher =  | date =  | accessdate = 16 September 2013 }}</ref>

==References==
{{Reflist|2}}

{{Lipopedia}}
[[Category:Lipopedia]]
[[Category:HDL]]
[[Category:Clinical trials]]
[[Category:HDLpedia]]