A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ascending, Subcutaneous, Single and Multiple Doses of SHP681 (Glucagon-like Peptide-2 [GLP-2] Analog-Fc Fusion) in Healthy Adult Participants

A Randomized, Double-blind, Placebo-controlled, Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ascending, Subcutaneous, Single and Multiple Doses of SHP681 (GLP-2 Analog-Fc Fusion) in Healthy Adult Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03859323

Enrollment

104

Registered

2019-03-01

Start date

2019-03-26

Completion date

2020-01-06

Last updated

2021-02-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Volunteers

Brief summary

The purpose of the study is to assess the safety and tolerability of single and multiple ascending subcutaneous (SC) doses of SHP681 in healthy adult participants.

Detailed description

The study consists of a single ascending dose (SAD) portion and a multiple ascending dose (MAD) portion. The study duration for the SAD portion of the study consists of a screening period of up to 28 days and 1 treatment period of 29 days. SAD portion of the study contains 5 cohorts and dose escalation will proceed sequentially to assess the following single SC doses of SHP681 or SHP681 matched placebo: 0.2 milligram per kilogram (mg/kg), 0.5 mg/kg, 1 mg/kg, 2 mg/kg, and 4 mg/kg. The study duration of the MAD portion comprises of a screening period up to 28 days and a treatment period of 57 days for each cohort. MAD portion of the study contains 6 cohorts and dose escalation will proceed sequentially to assess the following SC doses of SHP681 or SHP681 matched placebo: 0.2 mg/kg, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, and 4 mg/kg once weekly for 5 weeks till 5 cohorts and the 6th cohort will receive 4 mg/kg SHP681 or matched placebo every 2 weeks over a 6-week period (3 doses).

Interventions

DRUGSHP681

Participants will receive SC injection of SHP681 in the abdomen.

OTHERPlacebo

Participants will receive SC injection of placebo matched to SHP681 in the abdomen.

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 50 Years

Healthy volunteers

Yes

Inclusion criteria

* Ability to voluntarily provide written, signed, and dated informed consent to participate in the study. * An understanding, ability, and willingness to fully comply with study procedures and restrictions. * Age 18-50 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. * Considered healthy by the investigator. Healthy status is defined by absence of evidence of any active or chronic disease or condition based on 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 18.0 kilograms per square meter (kg/m\^2) and 30.0 kg/m\^2 inclusive with a body weight 50-100 kg (110-220 pounds \[lbs\]). This inclusion criterion will only be assessed at the first screening visit.

Exclusion criteria

* 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. * Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or render the participant unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures. * Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients. * Significant illness, as judged by the investigator, within 2 weeks of the first dose of investigational product. * Known history of alcohol or other substance abuse within the last year. * Donation of blood or blood products (example \[eg\], plasma or platelets) within 60 days prior to receiving the first dose of investigational product. * Within 30 days prior to the first dose of investigational product: 1. Have used an investigational product (if elimination half-life is less than (\<) 6 days, otherwise 5 half-lives). 2. Have been enrolled in a clinical study. 3. Have had any substantial changes in eating habits, as assessed by the investigator. * Use of dipeptidyl peptidase (DPP)-4 inhibitors within 30 days or 5 half-lives, whichever is greater, prior to administration of the investigational product. * Confirmed systolic blood pressure greater than (\>) 139 millimeters of mercury (mmHg) or \<89mmHg, and diastolic blood pressure \> 89mmHg or \<49 mmHg. * Twelve-lead ECG demonstrating corrected QT interval by Fredericia (QTcF) \>450 millisecond (msec) at screening. If QTcF exceeds 450 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF values should be used to determine the participant's eligibility. * Positive screen for alcohol or illicit drugs at screening or Day -1. * 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. (1 alcohol unit equal to \[=\] 1 beer or 1 wine (5 ounce \[oz\] 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 (eg, smoking or chewing) or other nicotine-containing products in any form (eg, gum, patch). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product. * Routine consumption of more than 2 units of caffeine per day or participants who experience headaches associated with caffeine withdrawal. (1 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, three 1 oz (85 g) chocolate bars. Decaffeinated coffee, tea, or cola are not considered to contain caffeine). * Prior screen failure (unless Sponsor approval is given), randomization, participation, or enrollment in this study or prior exposure to any GLP-2 analogs. * Unresected gastrointestinal (GI) polyp, known polyposis condition, or premalignant changes in the GI tract. * Any history of malignancy in the GI tract or treatment for any other malignancy in the previous 5 years. * Current use of any medication (including over-the-counter, herbal, or homeopathic preparations; with the exception of hormonal replacement therapy or hormonal contraceptives and occasional use of ibuprofen or acetaminophen and pre-approved medication for sedation or other medications required during or after the endoscopy). Current use is defined as use within 14 days of the first dose of investigational product. * Findings of subclinical hepatobiliary disease, such as gallstones, on abdominal ultrasound at screening as determined by the Investigator in consultation with the Medical Monitor.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	From start of study drug administration up to follow-up (Day 29 for SAD)	Adverse event (AE) was any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE was considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	From start of study drug administration up to follow-up (Day 57 for MAD)	AE was any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE was considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.
Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29	Day 29	Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in SAD at Day 29 were reported.
Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36	Day 36	Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in MAD at Day 36 were reported.
Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57	Day 57	Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in MAD at Day 57 were reported.

Secondary

Measure	Time frame	Description
Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD)	Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose	AUC0-inf of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Single Ascending Dose (SAD)	Pre-dose, 3, 6, 12, 24 hours post-dose	Cavg,0-24 of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 During Single Ascending Dose (SAD)	Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose	Lambda z of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUC0-inf (CL/F) of SHP681 During Single Ascending Dose (SAD)	Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose	CL/F of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 During Single Ascending Dose (SAD)	Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose	Vz/F of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Average Concentration From Time Zero to 24 Hours Post First Dose (Cavg,0-24) of SHP681 Post First Dose During Multiple Ascending Dose (MAD)	3, 6, 12, 24 hours post-dose on Day 1	Cavg,0-24 of SHP681 post first dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Pre-dose on Days 8, 15, 22 and 29	Ctrough of SHP681 for the First 5 cohorts and immediately before 2nd and 3rd dose of the 6th MAD cohort during MAD was reported.
Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29	Cmax of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29	Tlast of SHP681 post fifth dose during MAD was reported.
Terminal Half-life (t1/2) of SHP681 During Single Ascending Dose (SAD)	Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose	t1/2 of SHP681 during SAD was reported.
Area Under the Curve for the Defined Interval Between Doses (Only Calculated if Interpretable) (AUC0-tau) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29	AUC0-tau of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29	AUC0-last of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29	AUC0-inf of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD)	3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29	Cavg,0-24 of SHP681 during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29	t1/2 of SHP681 post fifth dose during MAD was reported.
First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29	Lambda z of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Apparent Total Body Clearance Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUCtau (CL/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29	CL/F of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29	Vz/F of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29	tmax of SHP681 post fifth dose during MAD was reported.
Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD)	Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose	Cmax of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD)	Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose	tlast of SHP681 during SAD was reported.
Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD)	Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose	tmax of SHP681 during SAD was reported.
Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 During Single Ascending Dose (SAD)	Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose	AUC0-last of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Countries

United States

Participant flow

Recruitment details

This study was conducted at single site in United States of America from 25 March 2019 (first participant first visit) and 06 January 2020 (last participant last visit).

Pre-assignment details

This study consisted of 2 parts: Part A - single ascending dose (SAD) and Part B - multiple ascending dose (MAD). A total of 104 participants were randomized in 2 parts with 30 participants to SAD and 74 participants to MAD, out of which 95 participants completed the study.

Participants by arm

Arm	Count
Part 1: Single Ascending Dose (SAD): Placebo Participants received single subcutaneous (SC) injection of placebo matched to SHP681 in the abdomen on Day 1.	5
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg Participants received single SC injection of 0.2 milligrams per kilogram (mg/kg) SHP681 in the abdomen on Day 1.	5
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg Participants received single SC injection of 0.5 mg/kg SHP681 in the abdomen on Day 1.	5
Part 1: Single Ascending Dose (SAD): 1 mg/kg Participants received single SC injection of 1 mg/kg SHP681 in the abdomen on Day 1.	5
Part 1: Single Ascending Dose (SAD): 2 mg/kg Participants received single SC injection of 2 mg/kg SHP681 in the abdomen on Day 1.	5
Part 1: Single Ascending Dose (SAD): 4 mg/kg Participants received single SC injection of 4 mg/kg SHP681 in the abdomen on Day 1.	5
Part 2: Multiple Ascending Dose (MAD): Placebo Participants received SC injection of placebo matched to SHP681 once weekly for 5 weeks in the abdomen up to Day 29.	12
Part 2: Multiple Ascending Dose (MAD): 0.2 mg/kg Participants received SC injection of 0.2 mg/kg SHP681 once weekly for 5 weeks in the abdomen up to Day 29.	10
Part 2: Multiple Ascending Dose (MAD): 0.5 mg/kg Participants received SC injection of 0.5 mg/kg SHP681 once weekly for 5 weeks in the abdomen up to Day 29.	10
Part 2: Multiple Ascending Dose (MAD): 1 mg/kg Participants received SC injection of 1 mg/kg SHP681 once weekly for 5 weeks in the abdomen up to Day 29.	10
Part 2: Multiple Ascending Dose (MAD): 2 mg/kg Participants received SC injection of 2 mg/kg SHP681 once weekly for 5 weeks in the abdomen up to Day 29.	10
Part 2: Multiple Ascending Dose (MAD): 4 mg/kg Participants received SC injection of 4 mg/kg SHP681 once weekly for 5 weeks in the abdomen up to Day 29.	12
Part 2: Multiple Ascending Dose (MAD): 4 mg/kg (Q2W) Participants received SC injection of placebo matched to SHP681 twice weekly (Q2W) for 5 weeks in the abdomen up to Day 29.	10
Total	104

Withdrawals & dropouts

Period	Reason	FG002	FG005	FG006	FG009	FG010	FG011	FG012
Overall Study	Lost to Follow-up	0	0	1	0	0	0	0
Overall Study	Pregnancy	0	0	0	1	0	0	0
Overall Study	Withdrawal by Subject	1	1	0	1	1	2	1

Baseline characteristics

Characteristic	Part 2: Multiple Ascending Dose (MAD): 1 mg/kg	Total	Part 2: Multiple Ascending Dose (MAD): 4 mg/kg (Q2W)	Part 2: Multiple Ascending Dose (MAD): 4 mg/kg	Part 2: Multiple Ascending Dose (MAD): 2 mg/kg	Part 1: Single Ascending Dose (SAD): Placebo	Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Part 1: Single Ascending Dose (SAD): 1 mg/kg	Part 1: Single Ascending Dose (SAD): 2 mg/kg	Part 1: Single Ascending Dose (SAD): 4 mg/kg	Part 2: Multiple Ascending Dose (MAD): Placebo	Part 2: Multiple Ascending Dose (MAD): 0.2 mg/kg	Part 2: Multiple Ascending Dose (MAD): 0.5 mg/kg
Age, Continuous	28.4 Years STANDARD_DEVIATION 9.52	32.0 Years STANDARD_DEVIATION 9.13	32.0 Years STANDARD_DEVIATION 8.45	29.8 Years STANDARD_DEVIATION 10.38	32.7 Years STANDARD_DEVIATION 9.38	33.6 Years STANDARD_DEVIATION 12.93	28.8 Years STANDARD_DEVIATION 7.6	38.0 Years STANDARD_DEVIATION 9.19	41.4 Years STANDARD_DEVIATION 8.32	33.0 Years STANDARD_DEVIATION 7.35	29.8 Years STANDARD_DEVIATION 3.96	31.2 Years STANDARD_DEVIATION 9.34	32.1 Years STANDARD_DEVIATION 8.63	32.5 Years STANDARD_DEVIATION 9.47
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	10 Participants	1 Participants	1 Participants	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants	94 Participants	9 Participants	11 Participants	7 Participants	5 Participants	5 Participants	5 Participants	5 Participants	5 Participants	4 Participants	11 Participants	9 Participants	10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	4 Participants	24 Participants	1 Participants	2 Participants	0 Participants	2 Participants	2 Participants	1 Participants	1 Participants	1 Participants	2 Participants	4 Participants	1 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	6 Participants	75 Participants	9 Participants	8 Participants	10 Participants	3 Participants	3 Participants	4 Participants	4 Participants	4 Participants	3 Participants	7 Participants	7 Participants	7 Participants
Sex: Female, Male Female	6 Participants	33 Participants	2 Participants	5 Participants	2 Participants	2 Participants	2 Participants	2 Participants	3 Participants	0 Participants	2 Participants	3 Participants	1 Participants	3 Participants
Sex: Female, Male Male	4 Participants	71 Participants	8 Participants	7 Participants	8 Participants	3 Participants	3 Participants	3 Participants	2 Participants	5 Participants	3 Participants	9 Participants	9 Participants	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk
deaths Total, all-cause mortality	0 / 5	0 / 5	0 / 5	0 / 5	0 / 5	0 / 5	0 / 12	0 / 10	0 / 10	0 / 10	0 / 10	0 / 12	0 / 10
other Total, other adverse events	3 / 5	3 / 5	2 / 5	4 / 5	3 / 5	2 / 5	9 / 12	8 / 10	3 / 10	6 / 10	5 / 10	9 / 12	8 / 10
serious Total, serious adverse events	0 / 5	0 / 5	0 / 5	0 / 5	0 / 5	0 / 5	0 / 12	0 / 10	0 / 10	0 / 10	1 / 10	0 / 12	0 / 10

Outcome results

Primary

Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36

Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in MAD at Day 36 were reported.

Time frame: Day 36

Population: SAS included participants who had received at least 1 dose of SHP681 or placebo. Here, the number of participants analyzed refer to the participants evaluable for this outcome measure.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36	0 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36	0 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36	1 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36	2 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36	0 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36	0 Participants
Part 2: Multiple Ascending Dose (MAD): 4 mg/kg (Q2W)	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36	0 Participants

Primary

Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57

Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in MAD at Day 57 were reported.

Time frame: Day 57

Population: SAS included participants who had received at least 1 dose of SHP681 or placebo. Here, the number of participants analyzed refer to the participants evaluable for this outcome measure.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57	0 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57	0 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57	1 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57	1 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57	1 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57	1 Participants
Part 2: Multiple Ascending Dose (MAD): 4 mg/kg (Q2W)	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57	0 Participants

Primary

Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29

Antibody testing was conducted using an electro chemiluminescent signal method. Number of participants with ADA to SHP681 in SAD at Day 29 were reported.

Time frame: Day 29

Population: SAS included participants who had received at least 1 dose of SHP681 or placebo. Here, the number of participants analyzed refer to the participants evaluable for this outcome measure.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29	0 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29	0 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29	0 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29	0 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29	0 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29	0 Participants

Primary

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)

AE was any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE was considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.

Time frame: From start of study drug administration up to follow-up (Day 57 for MAD)

Population: SAS included participants who had received at least 1 dose of SHP681 or placebo.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Mild TEAEs	9 Participants
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with TEAEs	9 Participants
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Serious TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Moderate TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Mild TEAEs	8 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Serious TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Moderate TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with TEAEs	8 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Serious TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with TEAEs	3 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Mild TEAEs	3 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Moderate TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Mild TEAEs	6 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with TEAEs	6 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Serious TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Moderate TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with TEAEs	5 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Mild TEAEs	5 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Moderate TEAEs	1 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Serious TEAEs	1 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with TEAEs	9 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Moderate TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Serious TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Mild TEAEs	9 Participants
Part 2: Multiple Ascending Dose (MAD): 4 mg/kg (Q2W)	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Moderate TEAEs	0 Participants
Part 2: Multiple Ascending Dose (MAD): 4 mg/kg (Q2W)	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Serious TEAEs	0 Participants
Part 2: Multiple Ascending Dose (MAD): 4 mg/kg (Q2W)	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Mild TEAEs	8 Participants
Part 2: Multiple Ascending Dose (MAD): 4 mg/kg (Q2W)	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with TEAEs	8 Participants
Part 2: Multiple Ascending Dose (MAD): 4 mg/kg (Q2W)	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)	Participants with Severe TEAEs	0 Participants

Primary

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)

Adverse event (AE) was any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE was considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.

Time frame: From start of study drug administration up to follow-up (Day 29 for SAD)

Population: SAS included participants who had received at least 1 dose of SHP681 or placebo.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with TEAEs	3 Participants
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Mild TEAEs	3 Participants
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Serious TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): Placebo	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Moderate TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Moderate TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Mild TEAEs	3 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with TEAEs	3 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Serious TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Mild TEAEs	2 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with TEAEs	2 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Serious TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Moderate TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with TEAEs	4 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Mild TEAEs	4 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Moderate TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Serious TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Serious TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Mild TEAEs	3 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with TEAEs	3 Participants
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Moderate TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with TEAEs	2 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Severe TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Mild TEAEs	2 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Moderate TEAEs	0 Participants
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)	Participants with Serious TEAEs	0 Participants

Secondary

Apparent Total Body Clearance Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUCtau (CL/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

CL/F of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29

Population: PK analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Apparent Total Body Clearance Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUCtau (CL/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.1225 L/h	Geometric Coefficient of Variation 38.5
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Apparent Total Body Clearance Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUCtau (CL/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.1366 L/h	Geometric Coefficient of Variation 53.5
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Apparent Total Body Clearance Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUCtau (CL/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.1141 L/h	Geometric Coefficient of Variation 21.3
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Apparent Total Body Clearance Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUCtau (CL/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.1226 L/h	Geometric Coefficient of Variation 35.5
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Apparent Total Body Clearance Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUCtau (CL/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.09547 L/h	Geometric Coefficient of Variation 27.3
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Apparent Total Body Clearance Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUCtau (CL/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.1100 L/h	Geometric Coefficient of Variation 19.6

Secondary

Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUC0-inf (CL/F) of SHP681 During Single Ascending Dose (SAD)

CL/F of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

Population: PK analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUC0-inf (CL/F) of SHP681 During Single Ascending Dose (SAD)	0.09810 Liter per hour (L/h)	Geometric Coefficient of Variation 22.6
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUC0-inf (CL/F) of SHP681 During Single Ascending Dose (SAD)	0.1188 Liter per hour (L/h)	Geometric Coefficient of Variation 42.9
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUC0-inf (CL/F) of SHP681 During Single Ascending Dose (SAD)	0.08856 Liter per hour (L/h)	Geometric Coefficient of Variation 20.6
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUC0-inf (CL/F) of SHP681 During Single Ascending Dose (SAD)	0.09909 Liter per hour (L/h)	Geometric Coefficient of Variation 33.7
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUC0-inf (CL/F) of SHP681 During Single Ascending Dose (SAD)	0.09689 Liter per hour (L/h)	Geometric Coefficient of Variation 25

Secondary

Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 During Single Ascending Dose (SAD)

Vz/F of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

Population: PK analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 During Single Ascending Dose (SAD)	12.01 Liter	Geometric Coefficient of Variation 37.2
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 During Single Ascending Dose (SAD)	15.02 Liter	Geometric Coefficient of Variation 54.7
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 During Single Ascending Dose (SAD)	12.75 Liter	Geometric Coefficient of Variation 27.8
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 During Single Ascending Dose (SAD)	14.05 Liter	Geometric Coefficient of Variation 35.8
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 During Single Ascending Dose (SAD)	12.98 Liter	Geometric Coefficient of Variation 27.2

Secondary

Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Vz/F of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	16.99 Liter	Geometric Coefficient of Variation 39.4
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	20.48 Liter	Geometric Coefficient of Variation 56.4
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	17.21 Liter	Geometric Coefficient of Variation 24
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	19.12 Liter	Geometric Coefficient of Variation 42.2
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	14.75 Liter	Geometric Coefficient of Variation 30.8
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	15.89 Liter	Geometric Coefficient of Variation 17.8

Secondary

Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD)

AUC0-inf of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

Population: PK analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD)	141.0 h*mcg/mL	Geometric Coefficient of Variation 36.9
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD)	288.6 h*mcg/mL	Geometric Coefficient of Variation 31.3
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD)	808.3 h*mcg/mL	Geometric Coefficient of Variation 16.4
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD)	1739 h*mcg/mL	Geometric Coefficient of Variation 25.8
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD)	3446 h*mcg/mL	Geometric Coefficient of Variation 23.5

Secondary

Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

AUC0-inf of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	203.4 h*mcg/mL	Geometric Coefficient of Variation 28.5
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	443.1 h*mcg/mL	Geometric Coefficient of Variation 33.5
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	1006 h*mcg/mL	Geometric Coefficient of Variation 16.3
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	2216 h*mcg/mL	Geometric Coefficient of Variation 29.6
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	5548 h*mcg/mL	Geometric Coefficient of Variation 22.8
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3277 h*mcg/mL	Geometric Coefficient of Variation 24.5

Secondary

Area Under the Curve for the Defined Interval Between Doses (Only Calculated if Interpretable) (AUC0-tau) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

AUC0-tau of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Area Under the Curve for the Defined Interval Between Doses (Only Calculated if Interpretable) (AUC0-tau) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	129.6 h*mcg/mL	Geometric Coefficient of Variation 33.2
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Area Under the Curve for the Defined Interval Between Doses (Only Calculated if Interpretable) (AUC0-tau) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	282.1 h*mcg/mL	Geometric Coefficient of Variation 36.2
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Area Under the Curve for the Defined Interval Between Doses (Only Calculated if Interpretable) (AUC0-tau) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	645.2 h*mcg/mL	Geometric Coefficient of Variation 18.7
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Area Under the Curve for the Defined Interval Between Doses (Only Calculated if Interpretable) (AUC0-tau) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	1344 h*mcg/mL	Geometric Coefficient of Variation 32.6
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Area Under the Curve for the Defined Interval Between Doses (Only Calculated if Interpretable) (AUC0-tau) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3297 h*mcg/mL	Geometric Coefficient of Variation 24.8
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Area Under the Curve for the Defined Interval Between Doses (Only Calculated if Interpretable) (AUC0-tau) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	2816 h*mcg/mL	Geometric Coefficient of Variation 25.9

Secondary

Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 During Single Ascending Dose (SAD)

AUC0-last of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

Population: PK analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 During Single Ascending Dose (SAD)	131.4 Hourmicrogram per milliliter (hmcg/mL)	Geometric Coefficient of Variation 43.7
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 During Single Ascending Dose (SAD)	282.1 Hourmicrogram per milliliter (hmcg/mL)	Geometric Coefficient of Variation 31.9
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 During Single Ascending Dose (SAD)	794.6 Hourmicrogram per milliliter (hmcg/mL)	Geometric Coefficient of Variation 16.3
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 During Single Ascending Dose (SAD)	1722 Hourmicrogram per milliliter (hmcg/mL)	Geometric Coefficient of Variation 25.6
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 During Single Ascending Dose (SAD)	3414 Hourmicrogram per milliliter (hmcg/mL)	Geometric Coefficient of Variation 23.5

Secondary

Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

AUC0-last of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	197.8 h*mcg/mL	Geometric Coefficient of Variation 29.1
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	435.2 h*mcg/mL	Geometric Coefficient of Variation 33.8
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	991.4 h*mcg/mL	Geometric Coefficient of Variation 16.3
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	2177 h*mcg/mL	Geometric Coefficient of Variation 29.9
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	5456 h*mcg/mL	Geometric Coefficient of Variation 22.8
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	3230 h*mcg/mL	Geometric Coefficient of Variation 24.7

Secondary

Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD)

Cavg,0-24 of SHP681 during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD)	0.6956 mcg/mL	Geometric Coefficient of Variation 42.3
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD)	1.683 mcg/mL	Geometric Coefficient of Variation 36.9
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD)	3.619 mcg/mL	Geometric Coefficient of Variation 20.8
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD)	7.942 mcg/mL	Geometric Coefficient of Variation 22.3
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD)	17.04 mcg/mL	Geometric Coefficient of Variation 23.4
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD)	7.006 mcg/mL	Geometric Coefficient of Variation 35.9

Secondary

Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Single Ascending Dose (SAD)

Cavg,0-24 of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: Pre-dose, 3, 6, 12, 24 hours post-dose

Population: PK analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Single Ascending Dose (SAD)	0.3733 Microgram per milliliter (mcg/mL)	Geometric Coefficient of Variation 227.3
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Single Ascending Dose (SAD)	0.6020 Microgram per milliliter (mcg/mL)	Geometric Coefficient of Variation 41.3
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Single Ascending Dose (SAD)	1.995 Microgram per milliliter (mcg/mL)	Geometric Coefficient of Variation 36
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Single Ascending Dose (SAD)	3.193 Microgram per milliliter (mcg/mL)	Geometric Coefficient of Variation 43.7
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Single Ascending Dose (SAD)	7.401 Microgram per milliliter (mcg/mL)	Geometric Coefficient of Variation 52.3

Secondary

Average Concentration From Time Zero to 24 Hours Post First Dose (Cavg,0-24) of SHP681 Post First Dose During Multiple Ascending Dose (MAD)

Cavg,0-24 of SHP681 post first dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: 3, 6, 12, 24 hours post-dose on Day 1

Population: PK analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Average Concentration From Time Zero to 24 Hours Post First Dose (Cavg,0-24) of SHP681 Post First Dose During Multiple Ascending Dose (MAD)	0.1716 mcg/mL	Geometric Coefficient of Variation 77.2
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Average Concentration From Time Zero to 24 Hours Post First Dose (Cavg,0-24) of SHP681 Post First Dose During Multiple Ascending Dose (MAD)	0.5091 mcg/mL	Geometric Coefficient of Variation 69.5
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Average Concentration From Time Zero to 24 Hours Post First Dose (Cavg,0-24) of SHP681 Post First Dose During Multiple Ascending Dose (MAD)	1.610 mcg/mL	Geometric Coefficient of Variation 72
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Average Concentration From Time Zero to 24 Hours Post First Dose (Cavg,0-24) of SHP681 Post First Dose During Multiple Ascending Dose (MAD)	2.108 mcg/mL	Geometric Coefficient of Variation 39.2
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Average Concentration From Time Zero to 24 Hours Post First Dose (Cavg,0-24) of SHP681 Post First Dose During Multiple Ascending Dose (MAD)	4.598 mcg/mL	Geometric Coefficient of Variation 40.4
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Average Concentration From Time Zero to 24 Hours Post First Dose (Cavg,0-24) of SHP681 Post First Dose During Multiple Ascending Dose (MAD)	5.660 mcg/mL	Geometric Coefficient of Variation 60.7

Secondary

First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 During Single Ascending Dose (SAD)

Lambda z of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

Population: PK analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 During Single Ascending Dose (SAD)	0.008156 One per hour (1/h)	Geometric Coefficient of Variation 23.6
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 During Single Ascending Dose (SAD)	0.007907 One per hour (1/h)	Geometric Coefficient of Variation 14.2
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 During Single Ascending Dose (SAD)	0.006945 One per hour (1/h)	Geometric Coefficient of Variation 12.8
Part 1: Single Ascending Dose (SAD): 1 mg/kg	First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 During Single Ascending Dose (SAD)	0.007050 One per hour (1/h)	Geometric Coefficient of Variation 10.4
Part 1: Single Ascending Dose (SAD): 2 mg/kg	First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 During Single Ascending Dose (SAD)	0.007011 One per hour (1/h)	Geometric Coefficient of Variation 15.2

Secondary

First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Lambda z of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.007215 1/h	Geometric Coefficient of Variation 9.4
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.006667 1/h	Geometric Coefficient of Variation 14.3
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.006633 1/h	Geometric Coefficient of Variation 6.3
Part 1: Single Ascending Dose (SAD): 1 mg/kg	First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.006416 1/h	Geometric Coefficient of Variation 8.7
Part 1: Single Ascending Dose (SAD): 2 mg/kg	First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.006473 1/h	Geometric Coefficient of Variation 9.8
Part 1: Single Ascending Dose (SAD): 4 mg/kg	First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.006922 1/h	Geometric Coefficient of Variation 5.5

Secondary

Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Cmax of SHP681 post fifth dose during MAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	0.9710 mcg/mL	Geometric Coefficient of Variation 38
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	2.215 mcg/mL	Geometric Coefficient of Variation 39.5
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	4.819 mcg/mL	Geometric Coefficient of Variation 19.6
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	10.38 mcg/mL	Geometric Coefficient of Variation 34.3
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	24.15 mcg/mL	Geometric Coefficient of Variation 28.2
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	14.45 mcg/mL	Geometric Coefficient of Variation 31.5

Secondary

Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD)

Cmax of SHP681 during SAD was reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.

Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

Population: Pharmacokinetic (PK) analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD)	0.8399 Micrograms per milliliter (mcg/mL)	Geometric Coefficient of Variation 73.2
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD)	1.515 Micrograms per milliliter (mcg/mL)	Geometric Coefficient of Variation 27.7
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD)	4.200 Micrograms per milliliter (mcg/mL)	Geometric Coefficient of Variation 26.8
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD)	8.647 Micrograms per milliliter (mcg/mL)	Geometric Coefficient of Variation 28.4
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD)	18.39 Micrograms per milliliter (mcg/mL)	Geometric Coefficient of Variation 25.2

Secondary

Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)

Ctrough of SHP681 for the First 5 cohorts and immediately before 2nd and 3rd dose of the 6th MAD cohort during MAD was reported.

Time frame: Pre-dose on Days 8, 15, 22 and 29

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1: Single Ascending Dose (SAD): Placebo	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 8	0.3523 mcg/mL	Geometric Coefficient of Variation 39.2
Part 1: Single Ascending Dose (SAD): Placebo	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 15	0.4688 mcg/mL	Geometric Coefficient of Variation 27.7
Part 1: Single Ascending Dose (SAD): Placebo	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 22	0.4593 mcg/mL	Geometric Coefficient of Variation 26.5
Part 1: Single Ascending Dose (SAD): Placebo	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 29	0.5288 mcg/mL	Geometric Coefficient of Variation 24.8
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 22	1.146 mcg/mL	Geometric Coefficient of Variation 25.1
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 29	1.203 mcg/mL	Geometric Coefficient of Variation 25.8
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 15	1.182 mcg/mL	Geometric Coefficient of Variation 30.6
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 8	0.8432 mcg/mL	Geometric Coefficient of Variation 28.2
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 29	2.659 mcg/mL	Geometric Coefficient of Variation 14.4
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 22	2.707 mcg/mL	Geometric Coefficient of Variation 12.3
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 15	2.332 mcg/mL	Geometric Coefficient of Variation 20.6
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 8	1.754 mcg/mL	Geometric Coefficient of Variation 11.9
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 8	4.062 mcg/mL	Geometric Coefficient of Variation 23.5
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 29	5.775 mcg/mL	Geometric Coefficient of Variation 27.4
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 15	5.312 mcg/mL	Geometric Coefficient of Variation 14.6
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 22	5.249 mcg/mL	Geometric Coefficient of Variation 18.8
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 22	13.09 mcg/mL	Geometric Coefficient of Variation 23
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 29	12.92 mcg/mL	Geometric Coefficient of Variation 26.7
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 15	9.888 mcg/mL	Geometric Coefficient of Variation 28.5
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 8	6.949 mcg/mL	Geometric Coefficient of Variation 20.9
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 29	3.109 mcg/mL	Geometric Coefficient of Variation 22.3
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)	Day 15	2.931 mcg/mL	Geometric Coefficient of Variation 22.9

Secondary

Terminal Half-life (t1/2) of SHP681 During Single Ascending Dose (SAD)

t1/2 of SHP681 during SAD was reported.

Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

Population: PK analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable.

Arm	Measure	Value (MEDIAN)
Part 1: Single Ascending Dose (SAD): Placebo	Terminal Half-life (t1/2) of SHP681 During Single Ascending Dose (SAD)	94.50 Hour
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Terminal Half-life (t1/2) of SHP681 During Single Ascending Dose (SAD)	88.40 Hour
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Terminal Half-life (t1/2) of SHP681 During Single Ascending Dose (SAD)	97.10 Hour
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Terminal Half-life (t1/2) of SHP681 During Single Ascending Dose (SAD)	95.40 Hour
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Terminal Half-life (t1/2) of SHP681 During Single Ascending Dose (SAD)	97.80 Hour

Secondary

Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

t1/2 of SHP681 post fifth dose during MAD was reported.

Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29

Arm	Measure	Value (MEDIAN)
Part 1: Single Ascending Dose (SAD): Placebo	Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	96.30 Hour
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	108.5 Hour
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	103.5 Hour
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	105.0 Hour
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	106.5 Hour
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	99.10 Hour

Secondary

Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD)

tmax of SHP681 during SAD was reported.

Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

Population: PK analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable.

Arm	Measure	Value (MEDIAN)
Part 1: Single Ascending Dose (SAD): Placebo	Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD)	24.00 Hour
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD)	72.00 Hour
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD)	48.00 Hour
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD)	72.00 Hour
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD)	72.00 Hour

Secondary

Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

tmax of SHP681 post fifth dose during MAD was reported.

Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29

Arm	Measure	Value (MEDIAN)
Part 1: Single Ascending Dose (SAD): Placebo	Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	72.00 Hour
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	36.00 Hour
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	48.00 Hour
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	48.00 Hour
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	48.00 Hour
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	72.00 Hour

Secondary

Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD)

tlast of SHP681 during SAD was reported.

Time frame: Pre-dose, 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 hours post-dose

Population: PK analysis set consisted of participants who received at least 1 dose of SHP681 and had at least 1 evaluable post-dose PK concentration value which was evaluable and interpretable.

Arm	Measure	Value (MEDIAN)
Part 1: Single Ascending Dose (SAD): Placebo	Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD)	335.0 Hour
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD)	504.0 Hour
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD)	673.0 Hour
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD)	672.0 Hour
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD)	672.0 Hour

Secondary

Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Tlast of SHP681 post fifth dose during MAD was reported.

Time frame: 3, 6, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672 and up to 768 hours post--dose on Day 29

Arm	Measure	Value (MEDIAN)
Part 1: Single Ascending Dose (SAD): Placebo	Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	504.0 Hour
Part 1: Single Ascending Dose (SAD): 0.2 mg/kg	Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	672.0 Hour
Part 1: Single Ascending Dose (SAD): 0.5 mg/kg	Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	672.5 Hour
Part 1: Single Ascending Dose (SAD): 1 mg/kg	Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	672.0 Hour
Part 1: Single Ascending Dose (SAD): 2 mg/kg	Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	672.0 Hour
Part 1: Single Ascending Dose (SAD): 4 mg/kg	Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)	672.0 Hour

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ascending, Subcutaneous, Single and Multiple Doses of SHP681 (Glucagon-like Peptide-2 [GLP-2] Analog-Fc Fusion) in Healthy Adult Participants

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36

Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57

Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD)

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD)

Apparent Total Body Clearance Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUCtau (CL/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Apparent Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as Dose Divided by AUC0-inf (CL/F) of SHP681 During Single Ascending Dose (SAD)

Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 During Single Ascending Dose (SAD)

Apparent Volume of Distribution Following Extravascular Administration Divided by the Fraction of Dose Absorbed Calculated as CL/F Divided by Lambda z (Vz/F) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD)

Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Area Under the Curve for the Defined Interval Between Doses (Only Calculated if Interpretable) (AUC0-tau) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 During Single Ascending Dose (SAD)

Area Under the Curve From the Time of Dosing to the Last Measurable Concentration (AUC0-last) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD)

Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Single Ascending Dose (SAD)

Average Concentration From Time Zero to 24 Hours Post First Dose (Cavg,0-24) of SHP681 Post First Dose During Multiple Ascending Dose (MAD)

First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 During Single Ascending Dose (SAD)

First Order Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD)

Observed Concentration at the End of Each Dosing Interval (Immediately Before Next Dose) (Ctrough) of SHP681 for the First 5 Cohorts and Immediately Before 2nd and 3rd Dose of the 6th MAD Cohort During Multiple Ascending Dose (MAD)

Terminal Half-life (t1/2) of SHP681 During Single Ascending Dose (SAD)

Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD)

Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)

Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD)

Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD)