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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SHP643 Prefilled Syringe (PFS) | Experimental | 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). |
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| SHP643 Autoinjector (AI) | Experimental | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SHP643 | Drug | Participants will receive injection of SHP643. |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of SHP643 in Plasma | AUC(0-last) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post dose |
| Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-Inf) of SHP643 in Plasma | AUC(0-infinity) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
| Maximum Observed Plasma Drug Concentration (Cmax) of SHP643 in Plasma | Cmax is the maximum observed plasma concentration of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
| Minimum Time to Reach (Tmax) in Maximum Observed Plasma Drug Concentration of SHP643 in Plasma | Tmax of of SHP643 in plasma was reported. | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
| Terminal Half-Life (T1/2) of SHP643 in Plasma | t1/2 of of SHP643 in plasma was reported. | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
| Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (CL/F) of SHP643 in Plasma |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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. |
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Inclusion Criteria:
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.
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.](streamdown:incomplete-link)
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Shire | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Pharmacology of Miami, LLC | Miami | Florida | 33014 | United States |
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| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
A total of 190 participants were enrolled and received the treatment. Out of which, 173 participants completed this study.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| FG001 | SHP643 Autoinjector (AI) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 29, 2019 | Nov 12, 2020 |
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CL/F of of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. |
| Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
| 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 | Vdz/F of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
| Terminal Elimination Rate Constant (Lambda z) of SHP643 in Plasma | Lambda z of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
| From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET]) |
| Number of Participants Who Developed Positive Antidrug Antibodies to SHP643 at Specified Time Points | Plasma samples were analyzed for presence of antidrug antibodies to SHP643. Participants who developed positive results for SHP643 antibodies were reported. | Day 1, 14, 28, 56 and 112 (End of Study/Early Termination [EOS/ET]) |
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).
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Safety analysis set consisted of all randomized participants who received the dose of SHP643.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| BG001 | 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). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of SHP643 in Plasma | AUC(0-last) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | day*microgram per milliliter (day*ug/mL) | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post dose |
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| Primary | Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-Inf) of SHP643 in Plasma | AUC(0-infinity) of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | day*μg/mL | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
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| Primary | Maximum Observed Plasma Drug Concentration (Cmax) of SHP643 in Plasma | Cmax is the maximum observed plasma concentration of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram per milliliter (ug/mL) | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
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| Primary | Minimum Time to Reach (Tmax) in Maximum Observed Plasma Drug Concentration of SHP643 in Plasma | Tmax of of SHP643 in plasma was reported. | 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. | Posted | Median | Full Range | day | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
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| Primary | Terminal Half-Life (T1/2) of SHP643 in Plasma | t1/2 of of SHP643 in plasma was reported. | 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. | Posted | Median | Full Range | day | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
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| Primary | Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (CL/F) of SHP643 in Plasma | CL/F of of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per day (L/day) | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
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| Primary | 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 | Vdz/F of SHP643 in plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters (L) | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
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| Primary | Terminal Elimination Rate Constant (Lambda z) of SHP643 in Plasma | Lambda z of SHP643 in Plasma was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | one per day (1/day) | Pre-dose, 8, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344, 2016, 2664 hours post-dose |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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. | Safety analysis set consisted of all randomized participants who received the dose of SHP643. | Posted | Count of Participants | Participants | From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET]) |
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| Secondary | Number of Participants Who Developed Positive Antidrug Antibodies to SHP643 at Specified Time Points | Plasma samples were analyzed for presence of antidrug antibodies to SHP643. Participants who developed positive results for SHP643 antibodies were reported. | Safety analysis set consisted of all randomized participants who received the dose of SHP643. | Posted | Count of Participants | Participants | Day 1, 14, 28, 56 and 112 (End of Study/Early Termination [EOS/ET]) |
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From start of study drug administration up to Day 112 (End of Study/Early Termination [EOS/ET])
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). | 0 | 94 | 2 | 94 | 0 | 94 |
| EG001 | 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). | 0 | 96 | 2 | 96 | 9 | 96 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 22.1 | Non-systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA 22.1 | Non-systematic Assessment |
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| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 22.1 | Non-systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA 22.1 | Non-systematic Assessment |
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| Abortion induced | Surgical and medical procedures | MedDRA 22.1 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site haemorrhage | General disorders | MedDRA 22.1 | Non-systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866-842-5335 | ClinicalTransparency@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 19, 2019 | Nov 12, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| C000596550 | lanadelumab |
| D020742 | rhoA GTP-Binding Protein |
| ID | Term |
|---|---|
| D020741 | rho GTP-Binding Proteins |
| D020559 | Monomeric GTP-Binding Proteins |
| D019204 | GTP-Binding Proteins |
| D020558 | GTP Phosphohydrolases |
| D017766 | Acid Anhydride Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D002352 | Carrier Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D047908 | Intracellular Signaling Peptides and Proteins |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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