A Study to Determine the Bioavailability of Lanadelumab (SHP643) Administered Subcutaneously With the Prefilled Syringe and the Autoinjector in Healthy Adult Volunteer Participants.
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate bioavailability of lanadelumab (SHP643) following a single, 2 milliliter (mL) subcutaneous (SC) dose of 300 milligrams (mg) delivered by prefilled syringe (PFS) or auto injector (AI) in healthy adult participants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SHP643 Prefilled Syringe (PFS) Participants will receive 300 milligram (mg) of SHP643 PFS Subcutaneous (SC) injection into the abdomen on Day 1 during the in-house period (Day 1 to Day 5). |
Drug: SHP643
Participants will receive injection of SHP643.
Other Names:
|
| Experimental: SHP643 Autoinjector (AI) Participants will receive 300 mg of SHP643 AI SC injection into the abdomen on Day 1 during the in-house period (Day 1 to Day 5). |
Drug: SHP643
Participants will receive injection of SHP643.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of SHP643 in Plasma [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post dose]
AUC(0-last) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
- Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-Inf) of SHP643 in Plasma [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose]
AUC(0-infinity) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
- Maximum Observed Plasma Drug Concentration (Cmax) of SHP643 in Plasma [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose]
Cmax is the maximum observed plasma concentration of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
- Minimum Time to Reach (Tmax) in Maximum Observed Plasma Drug Concentration of SHP643 in Plasma [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose]
Tmax of of SHP643 in plasma was reported.
- Terminal Half-Life (T1/2) of SHP643 in Plasma [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose]
t1/2 of of SHP643 in plasma was reported.
- Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (CL/F) of SHP643 in Plasma [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose]
CL/F of of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
- 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 [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose]
Vdz/F of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
- Terminal Elimination Rate Constant (Lambda z) of SHP643 in Plasma [Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose]
Lambda z of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Secondary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])]
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.
- Number of Participants Who Developed Positive Antidrug Antibodies to SHP643 at Specified Time Points [Day 1, 14, 28, 56 and 112 (End of Study/Early Termination [EOS/ET])]
Plasma samples were analyzed for presence of antidrug antibodies to SHP643. Participants who developed positive results for SHP643 antibodies were reported.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
An understanding, ability, and willingness to fully comply with study procedures and restrictions.
-
Ability to voluntarily provide written, signed, and dated informed consent to participate in the study.
-
Age 18-55, inclusive, at the time of consent. The date of signature of the informed consent is defined as the beginning of the screening period. This inclusion criterion will only be assessed at the first screening visit.
-
Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential.
-
Must be considered "healthy", per the investigator. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiogram (ECG), hematology, blood chemistry, and urinalysis.
-
Body mass index between 18.5-33 kilogram per square meter (kg/m^2), inclusive, with a body weight greater than or equal to (>=) 45 kilogram (kg) (99 pounds [lbs]). This inclusion criterion will only be assessed at the screening visit and on Day -1.
-
Willing and able to consume standardized meals during the confinement period of the study.
-
All participants will be required to consume the identical meals on study days when serial PK blood samples are collected
Exclusion Criteria:
-
Per the investigator, a history of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
-
Per the investigator, a current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the participant unlikely to complete the study, or any condition that present's undue risk from the investigational product or procedures.
-
Known or suspected intolerance or hypersensitivity to the investigational product, closelyrelated compounds, or any of the stated ingredients.
-
Significant illness, as judged by the investigator, within 2 weeks of the dose of investigational product.
-
Known history of alcohol or other substance abuse within the last year, per the investigator.
-
Donation of blood or blood products (e.g. plasma or platelets) within 60 days prior to receiving the dose of investigational product.
-
Within 30 days prior to the dose of investigational product.
-
Have used an investigational product (if elimination half-life is <6 days, otherwise 5 half lives).
-
Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this Shire-sponsored study.
-
Confirmed systolic blood pressure (BP) >139 millimeters of mercury (mmHg) or <89 mmHg, and diastolic BP >89 mmHg or <49 mmHg.
-
Twelve-lead ECG values demonstrating QTcF >450 milliseconds (msec) (males) or >470 msec (females) at the screening visit or Day -1. If QTcF exceeds 450 msec (males) or 470 msec (females), the ECG should be repeated 2 more times and the average of the 3 QTcF values should be used to determine the participants eligibility.
-
Positive screen for drugs of abuse and/or disallowed drugs (i.e. amphetamines, benzodiazepines, barbiturates, cocaine, opiates, phencyclidine) at screening, or drugs of abuse or alcohol on Day -1. This screen will include marijuana.
-
Male participants who consume more than 21 units of alcohol per week or 3 units per day. Female participants who consume more than 14 units of alcohol per week or 2 units per day. One alcohol unit=1 beer or 1 wine (5 ounces [oz) per 150 milliliter [mL]) or 1 liquor (1.5 oz/40 mL) or 0.75 oz alcohol.
-
Positive human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody screen.
-
Use of tobacco in any form (e.g. smoking or chewing) or other nicotine-containing products in any form (e.g. gum, patch, electronic). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the dose of investigational product.
-
Routine consumption of more than 2 units of caffeine per day or participants who experience caffeine withdrawal headaches. One caffeine unit is contained in the following items: one 6 oz (180 ml) cup of coffee, two 12 oz (360 ml) cans of cola, one 12 oz cup of tea, and three 1 oz (85 g) chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine).
-
Current use of any medication (including over-the-counter, herbal, or homeopathic preparations; with the exception of stable hormonal replacement therapy or hormonal contraceptives). Current use is defined as use within 14 days of the dose of investigational product. (Prior and Concomitant Treatment) for a list of permitted medications.
-
Abnormal laboratory values considered clinically significant, as determined by the investigator, at screening or Day -1.
-
History of any clinically significant surgery or procedure within 8 weeks of receiving the dose of investigational product, as determined by the investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Pharmacology of Miami, LLC | Miami | Florida | United States | 33014 |
Sponsors and Collaborators
- Shire
Investigators
- Study Director: Study Director, Shire
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- SHP643-102
Study Results
Participant Flow
| Recruitment Details | 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). |
|---|---|
| Pre-assignment Detail | A total of 190 participants were enrolled and received the treatment. Out of which, 173 participants completed this study. |
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Period Title: Overall Study | ||
| STARTED | 94 | 96 |
| COMPLETED | 84 | 89 |
| NOT COMPLETED | 10 | 7 |
Baseline Characteristics
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) | Total |
|---|---|---|---|
| Arm/Group Description | 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). | 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 of all reporting groups |
| Overall Participants | 94 | 96 | 190 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
39.6
(10.04)
|
42.1
(9.67)
|
40.8
(9.91)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
41
43.6%
|
55
57.3%
|
96
50.5%
|
| Male |
53
56.4%
|
41
42.7%
|
94
49.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
91
96.8%
|
92
95.8%
|
183
96.3%
|
| Not Hispanic or Latino |
3
3.2%
|
4
4.2%
|
7
3.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
13
13.8%
|
19
19.8%
|
32
16.8%
|
| White |
81
86.2%
|
77
80.2%
|
158
83.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of SHP643 in Plasma |
|---|---|
| Description | AUC(0-last) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. |
| Time Frame | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 89 | 89 |
| Geometric Mean (Geometric Coefficient of Variation) [day*microgram per milliliter (day*ug/mL)] |
348.9
(33.4)
|
376.5
(41.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SHP643 Prefilled Syringe (PFS), SHP643 Autoinjector (AI) |
|---|---|---|
| Comments | An analysis of variance was performed with the natural log-transformed PK parameters as the dependent variable and treatment group as a fixed effect variable. | |
| Type of Statistical Test | Other | |
| Comments | Analysis was performed for estimation of least square means only. Descriptive statistical analysis was the main analysis. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric least squares Means |
| Estimated Value | 1.079 | |
| Confidence Interval |
(2-Sided) 90% 0.986 to 1.181 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-Inf) of SHP643 in Plasma |
|---|---|
| Description | AUC(0-infinity) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. |
| Time Frame | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 89 | 89 |
| Geometric Mean (Geometric Coefficient of Variation) [day*μg/mL] |
352.5
(32.9)
|
380.3
(40.8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SHP643 Prefilled Syringe (PFS), SHP643 Autoinjector (AI) |
|---|---|---|
| Comments | An analysis of variance was performed with the natural log-transformed PK parameters as the dependent variable and treatment group as a fixed effect variable. | |
| Type of Statistical Test | Other | |
| Comments | Analysis was performed for estimation of least square means only. Descriptive statistical analysis was the main analysis. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric least squares Means |
| Estimated Value | 1.079 | |
| Confidence Interval |
(2-Sided) 90% 0.987 to 1.179 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maximum Observed Plasma Drug Concentration (Cmax) of SHP643 in Plasma |
|---|---|
| Description | Cmax is the maximum observed plasma concentration of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. |
| Time Frame | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 94 | 94 |
| Geometric Mean (Geometric Coefficient of Variation) [microgram per milliliter (ug/mL)] |
15.86
(40.6)
|
18.35
(48.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SHP643 Prefilled Syringe (PFS), SHP643 Autoinjector (AI) |
|---|---|---|
| Comments | An analysis of variance was performed with the natural log-transformed PK parameters as the dependent variable and treatment group as a fixed effect variable. | |
| Type of Statistical Test | Other | |
| Comments | Analysis was performed for estimation of least square means only. Descriptive statistical analysis was the main analysis. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric least squares Means |
| Estimated Value | 1.157 | |
| Confidence Interval |
(2-Sided) 90% 1.044 to 1.281 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Minimum Time to Reach (Tmax) in Maximum Observed Plasma Drug Concentration of SHP643 in Plasma |
|---|---|
| Description | Tmax of of SHP643 in plasma was reported. |
| Time Frame | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 94 | 94 |
| Median (Full Range) [day] |
4.00
|
4.00
|
| Title | Terminal Half-Life (T1/2) of SHP643 in Plasma |
|---|---|
| Description | t1/2 of of SHP643 in plasma was reported. |
| Time Frame | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 89 | 89 |
| Median (Full Range) [day] |
13.76
|
13.20
|
| Title | Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (CL/F) of SHP643 in Plasma |
|---|---|
| Description | CL/F of of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. |
| Time Frame | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 89 | 89 |
| Geometric Mean (Geometric Coefficient of Variation) [liter per day (L/day)] |
0.8511
(32.9)
|
0.7888
(40.8)
|
| Title | 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 |
|---|---|
| Description | Vdz/F of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. |
| Time Frame | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 89 | 89 |
| Geometric Mean (Geometric Coefficient of Variation) [Liters (L)] |
16.79
(31.6)
|
15.37
(42.7)
|
| Title | Terminal Elimination Rate Constant (Lambda z) of SHP643 in Plasma |
|---|---|
| Description | Lambda z of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. |
| Time Frame | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 89 | 89 |
| Geometric Mean (Geometric Coefficient of Variation) [one per day (1/day)] |
0.05070
(15.1)
|
0.05132
(22.1)
|
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
|---|---|
| Description | 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. |
| Time Frame | From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set consisted of all randomized participants who received the dose of SHP643. |
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 94 | 96 |
| Count of Participants [Participants] |
19
20.2%
|
30
31.3%
|
| Title | Number of Participants Who Developed Positive Antidrug Antibodies to SHP643 at Specified Time Points |
|---|---|
| Description | Plasma samples were analyzed for presence of antidrug antibodies to SHP643. Participants who developed positive results for SHP643 antibodies were reported. |
| Time Frame | Day 1, 14, 28, 56 and 112 (End of Study/Early Termination [EOS/ET]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set consisted of all randomized participants who received the dose of SHP643. |
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 94 | 96 |
| Participants with positive ADA: Day 1 |
1
1.1%
|
0
0%
|
| Participants with positive ADA: Day 14 |
0
0%
|
0
0%
|
| Participants with positive ADA: Day 28 |
1
1.1%
|
0
0%
|
| Participants with positive ADA: Day 56 |
0
0%
|
1
1%
|
| Participants with positive ADA: Day 112 (EOS/ET) |
0
0%
|
1
1%
|
Adverse Events
| Time Frame | From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET]) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) | ||
| Arm/Group Description | 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). | 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). | ||
All Cause Mortality |
||||
| SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/94 (0%) | 0/96 (0%) | ||
Serious Adverse Events |
||||
| SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/94 (2.1%) | 2/96 (2.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/94 (0%) | 0 | 1/96 (1%) | 1 |
| Infections and infestations | ||||
| Appendicitis | 1/94 (1.1%) | 1 | 0/96 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||
| Abortion spontaneous | 0/94 (0%) | 0 | 1/96 (1%) | 1 |
| Renal and urinary disorders | ||||
| Nephrolithiasis | 0/94 (0%) | 0 | 1/96 (1%) | 1 |
| Surgical and medical procedures | ||||
| Abortion induced | 1/94 (1.1%) | 1 | 0/96 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| SHP643 Prefilled Syringe (PFS) | SHP643 Autoinjector (AI) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/94 (0%) | 9/96 (9.4%) | ||
| General disorders | ||||
| Injection site haemorrhage | 0/94 (0%) | 0 | 9/96 (9.4%) | 9 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Shire |
| Phone | +1 866-842-5335 |
| ClinicalTransparency@takeda.com |
- SHP643-102