Phase 1
Completed N=104
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
Healthy Volunteers
Source: ClinicalTrials.gov NCT03859323 ↗
Enrolled (actual)
104
Serious AEs
1.0%
Results posted
Feb 2021
Primary outcomePrimary: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD) — 3; 3; 2; 4 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Single Ascending Dose (SAD) |
3; 3; 2; 4; 3; 2 | — |
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Based on Severity to SHP681 in Multiple Ascending Dose (MAD) |
9; 8; 3; 6; 5; 9 | — |
| PRIMARY Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Single Ascending Dose (SAD) at Day 29 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 36 |
0; 0; 1; 2; 0; 0 | — |
| PRIMARY Number of Participants With Anti-drug Antibody (ADA) to SHP681 in Multiple Ascending Dose (MAD) at Day 57 |
0; 0; 1; 1; 1; 1 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of SHP681 During Single Ascending Dose (SAD) |
0.8399; 1.515; 4.200; 8.647; 18.39 | — |
| SECONDARY Time of the Last Measurable Concentration (Tlast) of SHP681 During Single Ascending Dose (SAD) |
335.0; 504.0; 673.0; 672.0; 672.0 | — |
| SECONDARY Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 During Single Ascending Dose (SAD) |
24.00; 72.00; 48.00; 72.00; 72.00 | — |
| SECONDARY 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; 282.1; 794.6; 1722; 3414 | — |
| SECONDARY Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 During Single Ascending Dose (SAD) |
141.0; 288.6; 808.3; 1739; 3446 | — |
| SECONDARY Terminal Half-life (t1/2) of SHP681 During Single Ascending Dose (SAD) |
94.50; 88.40; 97.10; 95.40; 97.80 | — |
| SECONDARY Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Single Ascending Dose (SAD) |
0.3733; 0.6020; 1.995; 3.193; 7.401 | — |
| SECONDARY 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; 0.007907; 0.006945; 0.007050; 0.007011 | — |
| 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) |
0.09810; 0.1188; 0.08856; 0.09909; 0.09689 | — |
| 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) |
12.01; 15.02; 12.75; 14.05; 12.98 | — |
| 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) |
0.1716; 0.5091; 1.610; 2.108; 4.598; 5.660 | — |
| 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) |
0.3523; 0.8432; 1.754; 4.062; 6.949; 0.4688 | — |
| SECONDARY Maximum Concentration During the Dosing Interval Occurring at Tmax (Cmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD) |
0.9710; 2.215; 4.819; 10.38; 24.15; 14.45 | — |
| SECONDARY Time of the Last Measurable Concentration (Tlast) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD) |
504.0; 672.0; 672.5; 672.0; 672.0; 672.0 | — |
| SECONDARY Time of Maximum Observed Concentration Sampled During a Dosing Interval (Tmax) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD) |
72.00; 36.00; 48.00; 48.00; 48.00; 72.00 | — |
| 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) |
129.6; 282.1; 645.2; 1344; 3297; 2816 | — |
| 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) |
197.8; 435.2; 991.4; 2177; 5456; 3230 | — |
| SECONDARY Area Under the Curve Extrapolated to Infinity (AUC0-inf) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD) |
203.4; 443.1; 1006; 2216; 5548; 3277 | — |
| SECONDARY Average Concentration From Time Zero to 24 Hours Post Dose (Cavg,0-24) of SHP681 During Multiple Ascending Dose (MAD) |
0.6956; 1.683; 3.619; 7.942; 17.04; 7.006 | — |
| SECONDARY Terminal Half-life (t1/2) of SHP681 Post Fifth Dose During Multiple Ascending Dose (MAD) |
96.30; 108.5; 103.5; 105.0; 106.5; 99.10 | — |
| 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) |
0.007215; 0.006667; 0.006633; 0.006416; 0.006473; 0.006922 | — |
| 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) |
0.1225; 0.1366; 0.1141; 0.1226; 0.09547; 0.1100 | — |
| 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) |
16.99; 20.48; 17.21; 19.12; 14.75; 15.89 | — |
Eligibility Criteria
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:
- Have used an investigational product (if elimination half-life is less than ( ) 139 millimeters of mercury (mmHg) or 89mmHg or 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 (
Data sourced from ClinicalTrials.gov (NCT03859323). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.