A Randomized, Double-blind, Placebo-controlled, Ascending Dose, Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Intravenous and Subcutaneous Doses of Recombinant Human C1 Esterase Inhibitor in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- Recombinant human C1 esterase inhibitor
- Conditions
- Hereditary Angioedema (HAE)
- Sponsor
- Shire
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment-emergent Adverse Events (TEAEs ) Including Serious Adverse Events (SAEs)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This trial is looking to gain information about the safety and tolerability of an investigational treatment (SHP623) in healthy adult volunteers. This study will also collect pharmacokinetic data (how the body absorbs and breaks down the study drug).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Must be considered healthy. Healthy status is defined by absence of evidence of any active or chronic disease
- •Male, or non-pregnant, non-lactating female, who agrees to comply with any applicable contraceptive requirements of the protocol, or females of non-child-bearing potential.
- •Body mass index between 18.0 and 30.0 kg/m2 inclusive with a body weight \>50 kg (110 lbs.). This inclusion criterion will be assessed only at the first screening visit.
- •Hemoglobin ≥12.0g/ld.
Exclusion Criteria
- •Have a history of allergic reaction to C1 INH products (e.g. C1 Inhibitor \[Human\], Berinert \[C1 Estrace Inhibitor (Human)\] and C1 estrace \[recombinant\]
- •Known history of alcohol or other substance abuse within the last year.
- •Donation of blood or blood products within 60 days prior to receiving investigational product.
- •Current use of any medication except hormonal replacement therapy, hormonal contraceptives and occasional use of any over-the-counter non-steroidal anti-inflammatory drug (NSAID) or acetaminophen.
- •Have a history of hypercoagulability or other predisposition to thrombotic events.
Arms & Interventions
Treatment 1- 4
Treatment A: 9 Subjects will receive dose level I of SHP623 intravenously (IV). B: 9 Subjects will receive dose level I of SHP623 subcutaneously(SC).
Intervention: Recombinant human C1 esterase inhibitor
Treatment 1- 4
Treatment A: 9 Subjects will receive dose level I of SHP623 intravenously (IV). B: 9 Subjects will receive dose level I of SHP623 subcutaneously(SC).
Intervention: SHP623
Placebo
3 Subjects will receive placebo for each cohort
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants With Treatment-emergent Adverse Events (TEAEs ) Including Serious Adverse Events (SAEs)
Time Frame: From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. An AE was considered to be a TEAE in a specific treatment period of the study if the date and time of onset were after investigational product administration in that period and if it occurred less than equals to (\<=) Day 28 and was both not present at the start of that period and was not a chronic condition that was part of the participant's medical history, or it was present at the start of that period or as part of the participant's medical history but the severity or frequency increased during that period \<= Day 28. An SAE was defined as any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose.
Secondary Outcomes
- Maximum Observed Plasma Concentration (Cmax) of SHP623 Occurring at Time of Maximum Observed Concentration During a Dosing Interval (Tmax)(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Time of Maximum Plasma Concentration (Tmax) of SHP623 Sampled During a Dosing Interval(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Terminal Half-life (t1/2) of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC 0-inf) of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Area Under the Plasma Concentration Curve From Time Zero to 168 Hours Postdose (AUC 0-168) of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Total Body Clearance (CL) for Intravascular (IV) Administration of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Total Body Clearance for Extravascular Administration (CL/F) of SHP623 for Subcutaneous (SC) Administration(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Volume of Distribution Associated With the Terminal Slope (Vz) Following Intravenous (IV) Administration of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)
- Volume of Distribution Influenced by Fraction of Dose Absorbed (Vz/F) Following Extravascular Administration of SHP623(Pre-dose, 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 216, 312, 648 hours post-dose.)