Trial Outcomes & Findings for A Study to Determine the Bioavailability of Lanadelumab (SHP643) Administered Subcutaneously With the Prefilled Syringe and the Autoinjector in Healthy Adult Volunteer Participants. (NCT NCT03918239)
NCT ID: NCT03918239
Last Updated: 2020-12-08
Results Overview
AUC(0-last) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
COMPLETED
PHASE1
190 participants
Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post dose
2020-12-08
Participant Flow
This study was conducted at a single site in United States of America from 14 May 2019 (first participant first visit) to 13 November 2019 (last participant last visit).
A total of 190 participants were enrolled and received the treatment. Out of which, 173 participants completed this study.
Participant milestones
| Measure |
SHP643 Prefilled Syringe (PFS)
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Autoinjector (AI)
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Overall Study
STARTED
|
94
|
96
|
|
Overall Study
COMPLETED
|
84
|
89
|
|
Overall Study
NOT COMPLETED
|
10
|
7
|
Reasons for withdrawal
| Measure |
SHP643 Prefilled Syringe (PFS)
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Autoinjector (AI)
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
1
|
|
Overall Study
Pregnancy
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
|
Overall Study
positive urine drug screening results
|
4
|
1
|
Baseline Characteristics
A Study to Determine the Bioavailability of Lanadelumab (SHP643) Administered Subcutaneously With the Prefilled Syringe and the Autoinjector in Healthy Adult Volunteer Participants.
Baseline characteristics by cohort
| Measure |
SHP643 Prefilled Syringe (PFS)
n=94 Participants
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Autoinjector (AI)
n=96 Participants
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
Total
n=190 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.6 Years
STANDARD_DEVIATION 10.04 • n=5 Participants
|
42.1 Years
STANDARD_DEVIATION 9.67 • n=7 Participants
|
40.8 Years
STANDARD_DEVIATION 9.91 • n=5 Participants
|
|
Sex: Female, Male
Female
|
41 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
96 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
53 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
91 Participants
n=5 Participants
|
92 Participants
n=7 Participants
|
183 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
13 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
81 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
158 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post dosePopulation: Pharmacokinetic (PK) set was defined as all randomized participants who received the complete dose of SHP643 and had sufficient data to calculate at least one primary PK endpoint. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
AUC(0-last) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Outcome measures
| Measure |
SHP643 Autoinjector (AI)
n=89 Participants
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Prefilled Syringe (PFS)
n=89 Participants
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of SHP643 in Plasma
|
376.5 day*microgram per milliliter (day*ug/mL)
Geometric Coefficient of Variation 41.3
|
348.9 day*microgram per milliliter (day*ug/mL)
Geometric Coefficient of Variation 33.4
|
PRIMARY outcome
Timeframe: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dosePopulation: PK set was defined as all randomized participants who received the complete dose of SHP643 and had sufficient data to calculate at least one primary PK endpoint. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
AUC(0-infinity) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Outcome measures
| Measure |
SHP643 Autoinjector (AI)
n=89 Participants
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Prefilled Syringe (PFS)
n=89 Participants
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-Inf) of SHP643 in Plasma
|
380.3 day*μg/mL
Geometric Coefficient of Variation 40.8
|
352.5 day*μg/mL
Geometric Coefficient of Variation 32.9
|
PRIMARY outcome
Timeframe: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dosePopulation: PK set was defined as all randomized participants who received the complete dose of SHP643 and had sufficient data to calculate at least one primary PK endpoint. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Cmax is the maximum observed plasma concentration of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Outcome measures
| Measure |
SHP643 Autoinjector (AI)
n=94 Participants
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Prefilled Syringe (PFS)
n=94 Participants
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Maximum Observed Plasma Drug Concentration (Cmax) of SHP643 in Plasma
|
18.35 microgram per milliliter (ug/mL)
Geometric Coefficient of Variation 48.0
|
15.86 microgram per milliliter (ug/mL)
Geometric Coefficient of Variation 40.6
|
PRIMARY outcome
Timeframe: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dosePopulation: PPK set was defined as all randomized participants who received the complete dose of SHP643 and had sufficient data to calculate at least one primary PK endpoint. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Tmax of of SHP643 in plasma was reported.
Outcome measures
| Measure |
SHP643 Autoinjector (AI)
n=94 Participants
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Prefilled Syringe (PFS)
n=94 Participants
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Minimum Time to Reach (Tmax) in Maximum Observed Plasma Drug Concentration of SHP643 in Plasma
|
4.00 day
Interval 2.0 to 6.92
|
4.00 day
Interval 3.0 to 19.97
|
PRIMARY outcome
Timeframe: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dosePopulation: PK set was defined as all randomized participants who received the complete dose of SHP643 and had sufficient data to calculate at least one primary PK endpoint. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
t1/2 of of SHP643 in plasma was reported.
Outcome measures
| Measure |
SHP643 Autoinjector (AI)
n=89 Participants
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Prefilled Syringe (PFS)
n=89 Participants
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Terminal Half-Life (T1/2) of SHP643 in Plasma
|
13.20 day
Interval 8.21 to 40.1
|
13.76 day
Interval 9.7 to 20.5
|
PRIMARY outcome
Timeframe: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dosePopulation: PK set was defined as all randomized participants who received the complete dose of SHP643 and had sufficient data to calculate at least one primary PK endpoint. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
CL/F of of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Outcome measures
| Measure |
SHP643 Autoinjector (AI)
n=89 Participants
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Prefilled Syringe (PFS)
n=89 Participants
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (CL/F) of SHP643 in Plasma
|
0.7888 liter per day (L/day)
Geometric Coefficient of Variation 40.8
|
0.8511 liter per day (L/day)
Geometric Coefficient of Variation 32.9
|
PRIMARY outcome
Timeframe: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dosePopulation: PK set was defined as all randomized participants who received the complete dose of SHP643 and had sufficient data to calculate at least one primary PK endpoint. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Vdz/F of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Outcome measures
| Measure |
SHP643 Autoinjector (AI)
n=89 Participants
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Prefilled Syringe (PFS)
n=89 Participants
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Apparent Volume of Distribution Associated With the Terminal Slope Following Extravascular Administration Divided by the Fraction of Dose Absorbed (Vdz/F) of SHP643 in Plasma
|
15.37 Liters (L)
Geometric Coefficient of Variation 42.7
|
16.79 Liters (L)
Geometric Coefficient of Variation 31.6
|
PRIMARY outcome
Timeframe: Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dosePopulation: PK set was defined as all randomized participants who received the complete dose of SHP643 and had sufficient data to calculate at least one primary PK endpoint. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
Lambda z of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Outcome measures
| Measure |
SHP643 Autoinjector (AI)
n=89 Participants
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Prefilled Syringe (PFS)
n=89 Participants
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Terminal Elimination Rate Constant (Lambda z) of SHP643 in Plasma
|
0.05132 one per day (1/day)
Geometric Coefficient of Variation 22.1
|
0.05070 one per day (1/day)
Geometric Coefficient of Variation 15.1
|
SECONDARY outcome
Timeframe: From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])Population: Safety analysis set consisted of all randomized participants who received the dose of SHP643.
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product that did not necessarily have a causal relationship with the investigational product (IP) or medicinal product. A treatment-emergent AE (TEAE) was defined as any event emerging or manifesting at or after the initiation of treatment with an IP or medicinal product or any existing event that worsened in either intensity or frequency following exposure to the IP or medicinal product.
Outcome measures
| Measure |
SHP643 Autoinjector (AI)
n=96 Participants
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Prefilled Syringe (PFS)
n=94 Participants
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
|
30 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: Day 1, 14, 28, 56 and 112 (End of Study/Early Termination [EOS/ET])Population: Safety analysis set consisted of all randomized participants who received the dose of SHP643.
Plasma samples were analyzed for presence of antidrug antibodies to SHP643. Participants who developed positive results for SHP643 antibodies were reported.
Outcome measures
| Measure |
SHP643 Autoinjector (AI)
n=96 Participants
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Prefilled Syringe (PFS)
n=94 Participants
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Number of Participants Who Developed Positive Antidrug Antibodies to SHP643 at Specified Time Points
Participants with positive ADA: Day 1
|
0 Participants
|
1 Participants
|
|
Number of Participants Who Developed Positive Antidrug Antibodies to SHP643 at Specified Time Points
Participants with positive ADA: Day 14
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Developed Positive Antidrug Antibodies to SHP643 at Specified Time Points
Participants with positive ADA: Day 28
|
0 Participants
|
1 Participants
|
|
Number of Participants Who Developed Positive Antidrug Antibodies to SHP643 at Specified Time Points
Participants with positive ADA: Day 56
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Developed Positive Antidrug Antibodies to SHP643 at Specified Time Points
Participants with positive ADA: Day 112 (EOS/ET)
|
1 Participants
|
0 Participants
|
Adverse Events
SHP643 Prefilled Syringe (PFS)
SHP643 Autoinjector (AI)
Serious adverse events
| Measure |
SHP643 Prefilled Syringe (PFS)
n=94 participants at risk
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Autoinjector (AI)
n=96 participants at risk
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/94 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
1.0%
1/96 • Number of events 1 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
|
Infections and infestations
Appendicitis
|
1.1%
1/94 • Number of events 1 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
0.00%
0/96 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/94 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
1.0%
1/96 • Number of events 1 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/94 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
1.0%
1/96 • Number of events 1 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
|
Surgical and medical procedures
Abortion induced
|
1.1%
1/94 • Number of events 1 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
0.00%
0/96 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
Other adverse events
| Measure |
SHP643 Prefilled Syringe (PFS)
n=94 participants at risk
Participants received 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
SHP643 Autoinjector (AI)
n=96 participants at risk
Participants received 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house treatment period (Day 1 to Day 5).
|
|---|---|---|
|
General disorders
Injection site haemorrhage
|
0.00%
0/94 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
9.4%
9/96 • Number of events 9 • From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or 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