Trial Outcomes & Findings for A Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lanadelumab Administered Intravenously in Healthy Adult Volunteer Participants (NCT NCT04503603)
NCT ID: NCT04503603
Last Updated: 2022-03-07
Results Overview
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study that did not necessarily have a causal relationship with the treatment. TEAEs were events that occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs were reported.
COMPLETED
PHASE1
12 participants
From the first dose of study treatment up to the end of study (Day 112)
2022-03-07
Participant Flow
This study was conducted at 1 investigative site in the United States between 10 August 2020 (first participant first visit) and 23 December 2020 (last participant last visit).
A total of 12 healthy participants were enrolled and randomized to receive lanadelumab 300 milligrams (mg) or matching placebo in this study.
Participant milestones
| Measure |
Lanadelumab 300 mg
Participants received a single dose of lanadelumab 300 mg intravenous (IV) infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
Participants received a single dose of lanadelumab matching placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
3
|
|
Overall Study
COMPLETED
|
9
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lanadelumab Administered Intravenously in Healthy Adult Volunteer Participants
Baseline characteristics by cohort
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
n=3 Participants
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
34.3 years
STANDARD_DEVIATION 11.73 • n=5 Participants
|
42.0 years
STANDARD_DEVIATION 10.44 • n=7 Participants
|
36.3 years
STANDARD_DEVIATION 11.48 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
11 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
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 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: From the first dose of study treatment up to the end of study (Day 112)Population: The safety analysis set consisted of all participants who had started at least 1 dose of lanadelumab or placebo.
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study that did not necessarily have a causal relationship with the treatment. TEAEs were events that occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs were reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
n=3 Participants
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
|
7 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: From the first dose of study treatment up to the end of study (Day 112)Population: The safety analysis set consisted of all participants who had started at least 1 dose of lanadelumab or placebo.
Clinical laboratory assessment included hematology, clinical chemistry, coagulation, and urinalysis. Any changes in clinical laboratory results that were deemed clinically significant were judged by the investigator. The number of participants with clinically significant change from baseline in laboratory values were reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
n=3 Participants
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: From the first dose of study treatment up to the end of study (Day 112)Population: The safety analysis set consisted of all participants who had started at least 1 dose of lanadelumab or placebo.
Vital signs included blood pressure (systolic and diastolic), heart rate, and body temperature (oral). Any changes in vital signs that were deemed clinically significant were judged by the investigator. The number of participants with clinically significant change from baseline in vital signs were reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
n=3 Participants
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: From the first dose of study treatment up to the end of study (Day 112)Population: The safety analysis set consisted of all participants who had started at least 1 dose of lanadelumab or placebo.
12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. Any changes in ECG parameters that were deemed clinically significant were judged by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
n=3 Participants
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Pre-dose (Day 1) up to 2664 hours post-dosePopulation: The pharmacokinetic (PK) analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
AUC0-last for lanadelumab was reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration for Lanadelumab
|
32955 hour*microgram per milliliter (h*mcg/mL)
Geometric Coefficient of Variation 10.5
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (Day 1) up to 2664 hours post-dosePopulation: The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
AUC0-inf for lanadelumab was reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
AUC0-inf: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity for Lanadelumab
|
33305 h*mcg/mL
Geometric Coefficient of Variation 10.5
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (Day 1) up to 2664 hours post-dosePopulation: The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
Cmax1 following the first IV dose for lanadelumab was reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Cmax1: Maximum Observed Plasma Concentration Following the First IV Dose for Lanadelumab
|
75.6 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 16.1
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (Day 4) up to 2592 hours post-dosePopulation: The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
Cmax2 following the second IV dose for lanadelumab was reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Cmax2: Maximum Observed Plasma Concentration Following the Second IV Dose for Lanadelumab
|
120 mcg/mL
Geometric Coefficient of Variation 20.7
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (Day 1) up to 2664 hours post-dosePopulation: The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
Tmax1 following the first IV dose for lanadelumab was reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Tmax1: Minimum Observed Time to Reach the First Cmax1 for Lanadelumab
|
2.01 hours
Interval 2.0 to 4.01
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (Day 4) up to 2592 hours post-dosePopulation: The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
Tmax2 following the second IV dose for lanadelumab was reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Tmax2: Minimum Observed Time to Reach the Second Cmax2 for Lanadelumab
|
74.03 hours
Interval 72.92 to 76.02
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (Day 1) up to 2664 hours post-dosePopulation: The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
T1/2 is defined as the time required for the concentration of the drug to reach half of its original value. T1/2 for lanadelumab was reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Terminal Half-Life (T1/2) of Lanadelumab in Plasma
|
19.3 days
Interval 13.7 to 19.6
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (Day 1) up to 2664 hours post-dosePopulation: The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL for lanadelumab was reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Clearance (CL) of Lanadelumab in Plasma
|
18.1 milliliter per hour (mL/h)
Geometric Coefficient of Variation 10.4
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (Day 1) up to 2664 hours post-dosePopulation: The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss for lanadelumab was reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Vss: Volume of Distribution at Steady State in Plasma for Lanadelumab
|
8070 milliliter (mL)
Geometric Coefficient of Variation 19.5
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (Day 1) up to 2664 hours post-dosePopulation: The PK analysis set consisted of all participants who received at least one dose of the study drug and had at least one evaluable PK concentration post-dose.
Lambda z of Lanadelumab was reported.
Outcome measures
| Measure |
Lanadelumab 300 mg
n=9 Participants
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
First Order Elimination Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of Lanadelumab
|
9.90 Per hour (/h)
Geometric Coefficient of Variation 31.0
|
—
|
Adverse Events
Lanadelumab 300 mg
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Lanadelumab 300 mg
n=9 participants at risk
Participants received a single dose of lanadelumab 300 mg IV infusion on Day 1 followed by a second dose on Day 4.
|
Placebo
n=3 participants at risk
Participants received a single dose of placebo (normal saline) IV infusion on Day 1 followed by a second dose on Day 4.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
22.2%
2/9 • Number of events 2 • From the first dose of study treatment up to the end of study (Day 112)
|
0.00%
0/3 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Gastrointestinal disorders
Constipation
|
11.1%
1/9 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
33.3%
1/3 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/9 • From the first dose of study treatment up to the end of study (Day 112)
|
33.3%
1/3 • Number of events 2 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Gastrointestinal disorders
Nausea
|
11.1%
1/9 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
0.00%
0/3 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Gastrointestinal disorders
Vomiting
|
11.1%
1/9 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
0.00%
0/3 • From the first dose of study treatment up to the end of study (Day 112)
|
|
General disorders
Catheter site pain
|
11.1%
1/9 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
0.00%
0/3 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Infections and infestations
Cystitis
|
11.1%
1/9 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
0.00%
0/3 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
1/9 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
33.3%
1/3 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/9 • From the first dose of study treatment up to the end of study (Day 112)
|
33.3%
1/3 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
0.00%
0/9 • From the first dose of study treatment up to the end of study (Day 112)
|
33.3%
1/3 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Nervous system disorders
Headache
|
22.2%
2/9 • Number of events 4 • From the first dose of study treatment up to the end of study (Day 112)
|
33.3%
1/3 • Number of events 2 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Nervous system disorders
Paraesthesia
|
11.1%
1/9 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
0.00%
0/3 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
11.1%
1/9 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
0.00%
0/3 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/9 • From the first dose of study treatment up to the end of study (Day 112)
|
33.3%
1/3 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
11.1%
1/9 • Number of events 1 • From the first dose of study treatment up to the end of study (Day 112)
|
0.00%
0/3 • From the first dose of study treatment up to the end of study (Day 112)
|
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