Trial Outcomes & Findings for A Study of Two Different Formulations of LY3074828 in Healthy Participants (NCT NCT03188510)

Last Updated: 2024-01-25

Results Overview

PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (DN-AUC\[0-tlast\]) of LY3074828 was evaluated. Unit of measure expansion: microgram\*day per milliliter per milligram (µg\*day/mL/mg).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

54 participants

Primary outcome timeframe

Predose; 2, 6, 24, 72, 168, 240, 336, 504, 672, 1008, 1344, 1680 and 2016 hours postdose

Results posted on

2024-01-25

Participant Flow

Participant milestones

Participant milestones
Measure	Reference: 250 mg LY3074828 Participants received 250 mg LY3074828 lyophilized formulation, as 3 subcutaneous (SC) injections.	Test 1: 250 mg LY3074828 Participants received 250 mg LY3074828 solution formulation in 2 prefilled syringes (PFSs), as SC injections.	Test 2: 500 mg LY3074828 Participants received 500 mg LY3074828 solution formulation in 4 PFSs, as SC injections.
Overall Study STARTED	18	18	18
Overall Study Received at Least 1 Dose of Study Drug	18	18	18
Overall Study COMPLETED	18	17	18
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Reference: 250 mg LY3074828 Participants received 250 mg LY3074828 lyophilized formulation, as 3 subcutaneous (SC) injections.	Test 1: 250 mg LY3074828 Participants received 250 mg LY3074828 solution formulation in 2 prefilled syringes (PFSs), as SC injections.	Test 2: 500 mg LY3074828 Participants received 500 mg LY3074828 solution formulation in 4 PFSs, as SC injections.
Overall Study Inappropriate behavior with site staff	0	1	0

Baseline Characteristics

A Study of Two Different Formulations of LY3074828 in Healthy Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Reference: 250 mg LY3074828 n=18 Participants Participants received 250 mg LY3074828 lyophilized formulation, as 3 SC injections	Test 1: 250 mg LY3074828 n=18 Participants Participants received 250 mg LY3074828 solution formulation in 2 PFSs, as SC injections	Test 2: 500 mg LY3074828 n=18 Participants Participants received 500 mg LY3074828 solution formulation in 4 PFSs, as SC injections	Total n=54 Participants Total of all reporting groups
Age, Continuous	41.6 years STANDARD_DEVIATION 12.6 • n=99 Participants	42.1 years STANDARD_DEVIATION 11.0 • n=107 Participants	42.5 years STANDARD_DEVIATION 10.3 • n=206 Participants	42.0 years STANDARD_DEVIATION 11.1 • n=7 Participants
Sex: Female, Male Female	10 Participants n=99 Participants	8 Participants n=107 Participants	8 Participants n=206 Participants	26 Participants n=7 Participants
Sex: Female, Male Male	8 Participants n=99 Participants	10 Participants n=107 Participants	10 Participants n=206 Participants	28 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=99 Participants	4 Participants n=107 Participants	6 Participants n=206 Participants	14 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=99 Participants	14 Participants n=107 Participants	12 Participants n=206 Participants	40 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	9 Participants n=99 Participants	10 Participants n=107 Participants	7 Participants n=206 Participants	26 Participants n=7 Participants
Race (NIH/OMB) White	9 Participants n=99 Participants	8 Participants n=107 Participants	9 Participants n=206 Participants	26 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Region of Enrollment United States	18 Participants n=99 Participants	18 Participants n=107 Participants	18 Participants n=206 Participants	54 Participants n=7 Participants

PRIMARY outcome

Timeframe: Predose; 2, 6, 24, 72, 168, 240, 336, 504, 672, 1008, 1344, 1680 and 2016 hours postdose

Population: All enrolled participants who received at least one dose of LY3074828 and have evaluable PK data.

Outcome measures

Outcome measures
Measure	Reference: 250 mg LY3074828 n=18 Participants Participants received 250 mg LY3074828 lyophilized formulation, as 3 SC injections.	Test 1: 250 mg LY3074828 n=17 Participants Participants received 250 mg LY3074828 solution formulation in 2 PFSs, as SC injections.	Test 2: 500 mg LY3074828 n=18 Participants Participants received 500 mg LY3074828 solution formulation in 4 PFSs, as SC injections.
Pharmacokinetics (PK): Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (DN-AUC[0-tlast]) of LY3074828	1.06 µg*day/mL/mg Geometric Coefficient of Variation 27	1.03 µg*day/mL/mg Geometric Coefficient of Variation 40	1.04 µg*day/mL/mg Geometric Coefficient of Variation 32

PRIMARY outcome

Timeframe: Predose; 2, 6, 24, 72, 168, 240, 336, 504, 672, 1008, 1344, 1680 and 2016 hours postdose

Population: All enrolled participants who received at least one dose of LY3074828 and have evaluable PK data.

PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (DN-AUC\[0-∞\]) of LY3074828 was evaluated.

Outcome measures

Outcome measures
Measure	Reference: 250 mg LY3074828 n=18 Participants Participants received 250 mg LY3074828 lyophilized formulation, as 3 SC injections.	Test 1: 250 mg LY3074828 n=17 Participants Participants received 250 mg LY3074828 solution formulation in 2 PFSs, as SC injections.	Test 2: 500 mg LY3074828 n=18 Participants Participants received 500 mg LY3074828 solution formulation in 4 PFSs, as SC injections.
PK: Dose-normalized Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (DN-AUC[0-∞]) of LY3074828	1.07 µg.day/mL/mg Geometric Coefficient of Variation 27	1.05 µg.day/mL/mg Geometric Coefficient of Variation 40	1.05 µg.day/mL/mg Geometric Coefficient of Variation 32

SECONDARY outcome

Timeframe: Predose Day 1 Through Day 85

Population: All randomized participants who received at least one dose of LY3074828 and had evaluable anti-drug antibody measurement.

Number of participants with positive treatment emergent anti-drug antibodies was summarized by treatment group. A treatment-emergent ADA (TEADA) was defined as: having a negative ADA at baseline and an ADA titer greater than or equal to 1:20 (that is (i.e.), greater than 2-fold from the minimal required dilution of 1:10) any time post baseline (i.e., treatment-induced); or a 4-fold or greater change in ADA titer from baseline for participants that had a detectable ADA titer at baseline (i.e., treatment boosted).

Outcome measures

Outcome measures
Measure	Reference: 250 mg LY3074828 n=18 Participants Participants received 250 mg LY3074828 lyophilized formulation, as 3 SC injections.	Test 1: 250 mg LY3074828 n=17 Participants Participants received 250 mg LY3074828 solution formulation in 2 PFSs, as SC injections.	Test 2: 500 mg LY3074828 n=18 Participants Participants received 500 mg LY3074828 solution formulation in 4 PFSs, as SC injections.
Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA)	7 Participants	6 Participants	7 Participants

Adverse Events

Reference: 250 mg LY3074828

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Test 1: 250 mg LY3074828

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Test 2: 500 mg LY3074828

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	Reference: 250 mg LY3074828 n=18 participants at risk Participants received 250 mg LY3074828 lyophilized formulation, as 3 SC injections.	Test 1: 250 mg LY3074828 n=18 participants at risk Participants received 250 mg LY3074828 solution formulation in 2 PFSs, as SC injections.	Test 2: 500 mg LY3074828 n=18 participants at risk Participants received 500 mg LY3074828 solution formulation in 4 PFSs, as SC injections.
Gastrointestinal disorders Constipation	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Toothache	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
General disorders Feeling hot	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
General disorders Injection site haemorrhage	16.7% 3/18 • Number of events 4 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	16.7% 3/18 • Number of events 3 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
General disorders Injection site reaction	83.3% 15/18 • Number of events 32 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	83.3% 15/18 • Number of events 24 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	100.0% 18/18 • Number of events 55 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Limb discomfort	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Nervous system disorders Headache	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.
Surgical and medical procedures Tooth extraction	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.	0.00% 0/18 • Up to 85 days after administration of study drug All enrolled participants who received at least one dose of study drug.