Safety And Tolerability Of Multiple Doses Of PF-04950615 (RN316) In Subjects With Hypercholesterolemia

Study at a glance

From the registry record, last updated by the sponsor on 22 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Phase 1, Placebo-controlled, Randomized Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Following Multiple Intravenous Doses Of Pf-04950615 In Healthy Adult Subjects With Hypercholesterolemia

ClinicalTrials.gov ID

NCT01243151

Acronym / sponsor ID

B1481009

Conditions

Hypercholesterolemia, Dyslipidemia

Keywords

Hypercholesterolemia, Dyslipidemia, LDL, High Cholesterol, Japanese Volunteers, PF-04950615, RN316

Phase

Phase 1

Study type

Interventional

Recruitment status

Completed

Enrolment

68 participants (actual)

Lead sponsor

PfizerIndustry (pharma, biotech, devices)

Study start

Feb 2011 (actual)

Primary completion

Oct 2011 (actual)

Study completion

Oct 2011 (actual)

First posted

18 Nov 2010 (estimated)

Results

Posted 22 Jan 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Parallel groups

Masking

Double blind (participant, investigator)

Number of arms

5

Who may qualify

Ages

18 to 80 years

Sex

All

Healthy volunteers

Accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Dose Limiting and Intolerable Treatment-Related Adverse Events (AEs)

   Time frame: Baseline up to Follow-up period (Day 78)

   An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Dose limiting and intolerable treatment-related AEs were the AEs resulting from drug overdose, drug withdrawal, drug abuse, drug misuse, drug interactions, drug dependency, extravasation, exposure in utero, exposure during breast feeding.

2. Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Treatment-Related Adverse Events (AEs)

   Time frame: Baseline up to Follow-up period (Day 78)

   An AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to Day 78 that were absent before treatment or that worsened relative to pretreatment state.

3. Number of Participants With Adverse Events (AEs) by Severity

   Time frame: Baseline up to Follow-up period (Day 78)

   An AE was any untoward medical occurrence in a participant who received study drug. AE was assessed according to common terminology criteria for adverse events (CTCAE) version 4.0 severity grades- Grade 1: mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2: moderate (minimal, local or non invasive intervention indicated); Grade 3: severe (medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling); Grade 4: Life-threatening consequences; urgent intervention indicated and Grade 5: Death related to AE.

4. Number of Participants With Laboratory Test Abnormalities

   Time frame: Baseline up to Follow-up period (Day 78)

   Criteria: Haemoglobin(Hgb), hematocrit, RBC: <0.8*lower limit of normal(LLN),mean corpuscular volume, mean corpuscular Hgb concentration <0.9*LLN or>1.1*upper limit of normal(ULN), platelet<0.5*LLN or>1.75*ULN, WBC<0.6*LLN or>1.5*ULN, lymphocyte, neutrophil<0.8*LLN or>1.2*ULN, basophil, eosinophil, monocyte>1.2*ULN; bilirubin>1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, lactate dehydrogenase>3.0*ULN,total protein,albumin<0.8*LLN or>1.2*ULN; blood urea nitrogen, creatinine>1.3*ULN,uric acid>1.2*ULN;sodium<0.95*LLNor>1.05*ULN,potassium,chloride,calcium,bicarbonate<0.9*LLN or>1.1*ULN; glucose<0.6*LLN or >1.5*ULN, urine specific gravity<1.003 or>1.030,urine pH<4.5or>8,urine glucose, ketones, urine protein,urine blood/Hgb,urobilinogen,bilirubin,nitrite, leukocyte esterase>=1; urine RBC,WBC>=20,urine epithelial cells>=6,urine granular casts,hyaline casts>1,urine bacteria>20,partial thromboplastin time,prothrombin:>1.1*ULN.

5. Number of Participants With Clinically Relevant Changes in Vital Signs

   Time frame: Baseline up to Follow-up period (Day 78)

   Criteria for clinically relevant vital signs: supine and standing systolic blood pressure (SBP): less than (<) 90 millimeter of mercury (mmHg); supine and standing diastolic blood pressure (DBP): <50 mmHg. Maximum increase from baseline (IFB) or decrease from baseline (DFB) in supine and standing SBP: greater than or equal to (>=) 30 mmHg and maximum IFB or DFB in supine and standing DBP: >=20 mmHg. Supine pulse rate: <40 and greater than (>) 120 beats per minute (bpm); standing pulse rate: <40 and >140 bpm.

6. Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Parameters

   Time frame: Baseline up to Follow-up period (Day 78)

   Criteria for clinically relevant ECG parameters: PR interval: maximum IFB of >=25 percent or 50 percent; QRS complex: maximum IFB of >=25 or 50 percent; QTcF interval (Fridericia's Correction): maximum IFB of >=30 millisecond (msec) to <60 msec and maximum IFB of >=60 msec.

7. Number of Participants With Anti-drug Antibodies (ADA)

   Time frame: Baseline up to Follow-up period (Day 78)

   The number of participants with at least one positive ADA were summarized for each treatment arm. Participants with positive antibody titer of >4.32 milligram/milliliter (mg/mL) were considered as ADA positive.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2019.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 37994400Wang EQ, Kaila N, Plowchalk D, Gibiansky L, Yunis C, Sweeney K. Population PK/PD modeling of low-density lipoprotein cholesterol response in hypercholesterolemic participants following administration of bococizumab, a potent anti-PCSK9 monoclonal antibody. CPT Pharmacometrics Syst Pharmacol. 2023 Dec;12(12):2013-2026. doi: 10.1002/psp4.13050. Epub 2023 Nov 22.
• Derived from this study: PubMed 29037448Wan H, Gumbiner B, Joh T, Riel T, Udata C, Forgues P, Garzone PD. Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition with Bococizumab on Lipoprotein Particles in Hypercholesterolemic Subjects. Clin Ther. 2017 Nov;39(11):2243-2259.e5. doi: 10.1016/j.clinthera.2017.09.009. Epub 2017 Oct 14.
• Derived from this study: PubMed 28181260Udata C, Garzone PD, Gumbiner B, Joh T, Liang H, Liao KH, Williams JH, Meng X. A Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for Bococizumab, a Humanized Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, and Its Application in Early Clinical Development. J Clin Pharmacol. 2017 Jul;57(7):855-864. doi: 10.1002/jcph.867. Epub 2017 Feb 9.
• To obtain contact information for a study center near you, click here.Link provided by the sponsor.

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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.

9 sites in 1 country: see every site and its status.