Trial Outcomes & Findings for Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Recombinant Human C1 Esterase Inhibitor in Healthy Adult Subjects (NCT NCT02663687)
NCT ID: NCT02663687
Last Updated: 2021-06-03
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
48 participants
Primary outcome timeframe
From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
Results posted on
2021-06-03
Participant Flow
The study was conducted at a single center in the United States between 19 February 2016 (first participant first visit) and 05 December 2016 (last participant last visit).
A total of 48 participants were screened, randomized and received at least one dose of treatment.
Participant milestones
| Measure |
Placebo
Participants received placebo matched to SHP623 intravenous (IV) and subcutaneous (SC) administration in 1:3 ratio for each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an subcutaneous SC dose.
|
2000 U SHP623
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an subcutaneous SC dose.
|
3000 U SHP623
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an subcutaneous SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an subcutaneous SC dose.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
12
|
9
|
9
|
9
|
9
|
|
Overall Study
Treatment Period 1 (IV)
|
12
|
9
|
9
|
9
|
9
|
|
Overall Study
Treatment Period 2 (SC)
|
10
|
9
|
8
|
9
|
9
|
|
Overall Study
COMPLETED
|
10
|
9
|
8
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo matched to SHP623 intravenous (IV) and subcutaneous (SC) administration in 1:3 ratio for each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an subcutaneous SC dose.
|
2000 U SHP623
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an subcutaneous SC dose.
|
3000 U SHP623
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an subcutaneous SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an subcutaneous SC dose.
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Other
|
1
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Recombinant Human C1 Esterase Inhibitor in Healthy Adult Subjects
Baseline characteristics by cohort
| Measure |
Placebo
n=12 Participants
Participants received placebo matched to SHP623 intravenous and subcutaneous administration in 1:3 ratio for each cohort during treatment period 1 and 2 for 28 days respectively with 28 days interval between intravenous (IV) and subcutaneous (SC) dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=9 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 and 2 for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
2000 U SHP623
n=9 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 and 2 for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 and 2 for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 and 2 for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
Total
n=48 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
36.3 Years
STANDARD_DEVIATION 7.93 • n=5 Participants
|
40.7 Years
STANDARD_DEVIATION 7.25 • n=7 Participants
|
36.8 Years
STANDARD_DEVIATION 7.08 • n=5 Participants
|
38.0 Years
STANDARD_DEVIATION 10.49 • n=4 Participants
|
35.7 Years
STANDARD_DEVIATION 8.63 • n=21 Participants
|
37.4 Years
STANDARD_DEVIATION 8.17 • n=8 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
20 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
28 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)Population: Safety analysis set consisted of all participants who were administered at least 1 dose of investigational product.
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.
Outcome measures
| Measure |
2000 U SHP623
n=9 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=12 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs ) Including Serious Adverse Events (SAEs)
Any TEAE
|
4 Participants
|
3 Participants
|
8 Participants
|
8 Participants
|
4 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs ) Including Serious Adverse Events (SAEs)
Serious TEAE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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.Population: Pharmacokinetic (PK) set consisted of all participants in the safety analysis set for whom the primary PK data were considered sufficient and interpretable.
Cmax of SHP623 recombinant human C1 esterase inhibitor (rC1 INH) antigen at Tmax was calculated based on observed concentration-versus-time data. Cmax at Tmax of SHP623 for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group.
Outcome measures
| Measure |
2000 U SHP623
n=9 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=9 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of SHP623 Occurring at Time of Maximum Observed Concentration During a Dosing Interval (Tmax)
Intravenous (IV)
|
130.367 microgram per milliliter (mcg/ml)
Standard Deviation 31.3581
|
160.556 microgram per milliliter (mcg/ml)
Standard Deviation 22.1083
|
307.000 microgram per milliliter (mcg/ml)
Standard Deviation 54.6374
|
47.911 microgram per milliliter (mcg/ml)
Standard Deviation 14.5979
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) of SHP623 Occurring at Time of Maximum Observed Concentration During a Dosing Interval (Tmax)
Subcutaneous (SC)
|
15.694 microgram per milliliter (mcg/ml)
Standard Deviation 4.2062
|
16.318 microgram per milliliter (mcg/ml)
Standard Deviation 4.5612
|
32.056 microgram per milliliter (mcg/ml)
Standard Deviation 8.7727
|
4.248 microgram per milliliter (mcg/ml)
Standard Deviation 1.7445
|
—
|
SECONDARY outcome
Timeframe: 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.Population: PK set consisted of all participants in the safety analysis set for whom the primary PK data were considered sufficient and interpretable.
Tmax of SHP623 (rC1 INH) antigen was calculated based on observed concentration-versus-time data. Tmax of SHP623 for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group.
Outcome measures
| Measure |
2000 U SHP623
n=9 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=9 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of SHP623 Sampled During a Dosing Interval
Intravenous (IV)
|
0.250 hour (h)
Interval 0.25 to 1.0
|
0.250 hour (h)
Interval 0.25 to 1.0
|
0.500 hour (h)
Interval 0.25 to 1.0
|
0.250 hour (h)
Interval 0.25 to 0.25
|
—
|
|
Time of Maximum Plasma Concentration (Tmax) of SHP623 Sampled During a Dosing Interval
Subcutaneous (SC)
|
36.000 hour (h)
Interval 24.0 to 72.0
|
48.000 hour (h)
Interval 36.0 to 96.0
|
48.000 hour (h)
Interval 36.0 to 96.0
|
72.000 hour (h)
Interval 36.0 to 144.0
|
—
|
SECONDARY outcome
Timeframe: 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.Population: PK set consisted of all participants in the safety analysis set for whom the primary PK data were considered sufficient and interpretable.
t1/2 is the time required for the concentration of the drug to reach half of its original value. t1/2 of SHP623 (rC1 INH) antigen for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group.
Outcome measures
| Measure |
2000 U SHP623
n=9 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=9 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Terminal Half-life (t1/2) of SHP623
Intravenous (IV)
|
40.2 hour (h)
Interval 30.2 to 45.8
|
38.2 hour (h)
Interval 33.6 to 48.2
|
38.9 hour (h)
Interval 31.7 to 48.2
|
28.8 hour (h)
Interval 24.6 to 38.6
|
—
|
|
Terminal Half-life (t1/2) of SHP623
Subcutaneous (SC)
|
49.8 hour (h)
Interval 42.4 to 65.9
|
59.5 hour (h)
Interval 46.3 to 71.7
|
51.8 hour (h)
Interval 35.8 to 63.3
|
51.8 hour (h)
Interval 34.0 to 80.4
|
—
|
SECONDARY outcome
Timeframe: 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.Population: PK set consisted of all participants in the safety analysis set for whom the primary PK data were considered sufficient and interpretable.
AUC 0-inf is the area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration. AUC 0-inf of SHP623 (rC1 INH) antigen was calculated from observed concentration-versus-time data. AUC 0-inf of SHP623 for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group. The unit of measure is hour\*microgram per milliliter (hr\*mcg/ml).
Outcome measures
| Measure |
2000 U SHP623
n=9 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=9 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC 0-inf) of SHP623
Intravenous (IV)
|
2941.364 hr*mcg/ml
Standard Deviation 348.6029
|
4278.273 hr*mcg/ml
Standard Deviation 663.0496
|
8282.120 hr*mcg/ml
Standard Deviation 1118.0116
|
1114.535 hr*mcg/ml
Standard Deviation 368.6962
|
—
|
|
Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC 0-inf) of SHP623
Subcutaneous (SC)
|
1653.875 hr*mcg/ml
Standard Deviation 318.0261
|
2304.409 hr*mcg/ml
Standard Deviation 590.0275
|
4174.091 hr*mcg/ml
Standard Deviation 854.5110
|
594.741 hr*mcg/ml
Standard Deviation 101.0006
|
—
|
SECONDARY outcome
Timeframe: 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.Population: PK set consisted of all participants in the safety analysis set for whom the primary PK data were considered sufficient and interpretable.
AUC 0-168 is the area under the concentration curve over the interval from 0 to 168 hours after dosing of SHP623. AUC 0-168 of SHP623 (rC1 INH) was calculated based on observed concentration-versus-time data. AUC 0-168 of SHP623 for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group. The unit of measure is hour\*microgram per milliliter (hr\*mcg/ml).
Outcome measures
| Measure |
2000 U SHP623
n=9 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=9 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Area Under the Plasma Concentration Curve From Time Zero to 168 Hours Postdose (AUC 0-168) of SHP623
Intravenous (IV)
|
2823.169 hr*mcg/ml
Standard Deviation 311.8634
|
4083.493 hr*mcg/ml
Standard Deviation 623.9060
|
7893.069 hr*mcg/ml
Standard Deviation 1010.5182
|
1069.451 hr*mcg/ml
Standard Deviation 365.0676
|
—
|
|
Area Under the Plasma Concentration Curve From Time Zero to 168 Hours Postdose (AUC 0-168) of SHP623
Subcutaneous (SC)
|
1414.762 hr*mcg/ml
Standard Deviation 328.9591
|
1792.962 hr*mcg/ml
Standard Deviation 488.0679
|
3386.375 hr*mcg/ml
Standard Deviation 790.1633
|
407.936 hr*mcg/ml
Standard Deviation 149.3221
|
—
|
SECONDARY outcome
Timeframe: 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.Population: PK set consisted of all participants in the safety analysis set for whom the primary PK data were considered sufficient and interpretable.
AUClast is the area under the curve from the time 0 to the last measurable concentration of SHP623 (rC1 INH), which was calculated from observed concentration-versus-time data. AUClast of SHP623 for both treatment period 1 (IV) and treatment period 2 (SC) was presented in the categories for each dosing group. The unit of measure is hour\*microgram per milliliter (hr\*mcg/ml).
Outcome measures
| Measure |
2000 U SHP623
n=9 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=9 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of SHP623
Intravenous (IV)
|
2868.736 hr*mcg/ml
Standard Deviation 344.7756
|
4174.135 hr*mcg/ml
Standard Deviation 664.8862
|
8168.337 hr*mcg/ml
Standard Deviation 1127.0107
|
1054.798 hr*mcg/ml
Standard Deviation 369.5553
|
—
|
|
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) of SHP623
Subcutaneous (SC)
|
1518.124 hr*mcg/ml
Standard Deviation 341.5602
|
2159.527 hr*mcg/ml
Standard Deviation 599.1840
|
4040.772 hr*mcg/ml
Standard Deviation 845.6065
|
401.030 hr*mcg/ml
Standard Deviation 147.1284
|
—
|
SECONDARY outcome
Timeframe: 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.Population: PK set consisted of all participants in the safety analysis set for whom the primary PK data were considered sufficient and interpretable.
CL is the total body clearance of SHP623 for IV administration. The unit of measurement is unit per hour\*microgram per milliliter \[U/(hr\*mcg/ml)\].
Outcome measures
| Measure |
2000 U SHP623
n=9 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=9 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Total Body Clearance (CL) for Intravascular (IV) Administration of SHP623
|
0.688 U/(hr*mcg/ml)
Standard Deviation 0.0802
|
0.718 U/(hr*mcg/ml)
Standard Deviation 0.1233
|
0.614 U/(hr*mcg/ml)
Standard Deviation 0.0857
|
0.961 U/(hr*mcg/ml)
Standard Deviation 0.2229
|
—
|
SECONDARY outcome
Timeframe: 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.Population: PK set consisted of all participants in the safety analysis set for whom the primary PK data were considered sufficient and interpretable.
Vz is the volume of distribution associated with the terminal slope following IV administration. Vz was calculated for SHP 623 (rC1 INH) antigen from observed concentration-versus-time data. The unit of measure is unit per microgram per milliliter \[U/(mcg/ml)\].
Outcome measures
| Measure |
2000 U SHP623
n=9 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=9 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Volume of Distribution Associated With the Terminal Slope (Vz) Following Intravenous (IV) Administration of SHP623
|
37.284 U/(mcg/ml)
Standard Deviation 4.8077
|
40.794 U/(mcg/ml)
Standard Deviation 6.9950
|
35.684 U/(mcg/ml)
Standard Deviation 4.6175
|
42.600 U/(mcg/ml)
Standard Deviation 10.7552
|
—
|
SECONDARY outcome
Timeframe: 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.Population: PK set consisted of all participants in the safety analysis set for whom the primary PK data were considered sufficient and interpretable.
CL/F is the total body clearance for extravascular administration of SHP623 for SC administration divided by the fraction of dose absorbed. CL/F of SHP623 (rC1 INH) was calculated based on observed concentration-versus-time data. The unit of measure is unit per hour\*microgram per milliliter \[U/(hr\*mcg/ml)\].
Outcome measures
| Measure |
2000 U SHP623
n=8 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=6 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Total Body Clearance for Extravascular Administration (CL/F) of SHP623 for Subcutaneous (SC) Administration
|
1.250 U/(hr*mcg/ml)
Standard Deviation 0.2445
|
1.399 U/(hr*mcg/ml)
Standard Deviation 0.4512
|
1.254 U/(hr*mcg/ml)
Standard Deviation 0.3199
|
1.723 U/(hr*mcg/ml)
Standard Deviation 0.2965
|
—
|
SECONDARY outcome
Timeframe: 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.Population: PK set consisted of all participants in the safety analysis set for whom the primary PK data were considered sufficient and interpretable.
Vz/F is the volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed for subcutaneous (SC) administration. Vz/F of SHP623 (rC1 INH) were calculated from observed concentration-versus-time data. The unit of measure is unit per microgram per milliliter \[U/(mcg/ml)\].
Outcome measures
| Measure |
2000 U SHP623
n=8 Participants
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 Participants
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 Participants
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=6 Participants
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Volume of Distribution Influenced by Fraction of Dose Absorbed (Vz/F) Following Extravascular Administration of SHP623
|
94.861 U/(mcg/ml)
Standard Deviation 27.1022
|
121.511 U/(mcg/ml)
Standard Deviation 37.3158
|
94.463 U/(mcg/ml)
Standard Deviation 30.0244
|
133.585 U/(mcg/ml)
Standard Deviation 48.5385
|
—
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
1000 U SHP623
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
2000 U SHP623
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
3000 U SHP623
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
5000 U SHP623
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=12 participants at risk
Participants received placebo matched to SHP623 intravenous (IV) and subcutaneous (SC) administration in 1:3 ratio for each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
1000 U SHP623
n=9 participants at risk
Participants received 1000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
2000 U SHP623
n=9 participants at risk
Participants received 2000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
3000 U SHP623
n=9 participants at risk
Participants received 3000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
5000 U SHP623
n=9 participants at risk
Participants received 5000 unit (U) of SHP623 in each cohort during treatment period 1 (IV) and treatment period 2 (SC) for 28 days respectively with 28 days interval between IV and SC dosing in the following order: once as an IV dose and once as an SC dose.
|
|---|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/12 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/12 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Gastrointestinal disorders
Diarrhoea
|
8.3%
1/12 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/12 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/12 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/12 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
22.2%
2/9 • Number of events 2 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
General disorders
Injection site pain
|
8.3%
1/12 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
22.2%
2/9 • Number of events 2 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Investigations
Liver function test abnormal
|
8.3%
1/12 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Nervous system disorders
Headache
|
41.7%
5/12 • Number of events 6 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
33.3%
3/9 • Number of events 3 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
22.2%
2/9 • Number of events 2 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
44.4%
4/9 • Number of events 4 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Nervous system disorders
Somnolence
|
8.3%
1/12 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/12 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/12 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/12 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
11.1%
1/9 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
8.3%
1/12 • Number of events 1 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
0.00%
0/9 • From the start of study treatment up to 28 days after the last dose of the study treatment (up to 56 days)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonmentor termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER