Humalog and Humulin-R (recombinant human insulin) are Food and Drug Administration (FDA) approved medications for the treatment of diabetes mellitus. Recombinant human hyaluronidase PH20 (rHuPH20) is approved by the FDA for use as an aid in the absorption and dispersion of other injectable drugs. In this study, rHuPH20 will be co-administered with both Humalog and Humulin-R in order to determine if it improves the absorption of these insulins to more closely mimic the body's natural increase in insulin in response to a meal.

Participants received all 4 interventions in the same order.

Dose-finding visits were conducted to identify the appropriate dose of Humalog and Humulin-R. For each Humalog dose-finding visit, a total of 24 U of rHuPH20 was injected SC per unit of Humalog, corresponding to a mass concentration of 18.2 micrograms per milliliter (μg/mL) rHuPH20 (at final concentration of 91 U/mL of Humalog). For each Humulin-R dose-finding visit, a total of 24 U of rHuPH20 was injected SC per unit of Humulin-R, corresponding to a mass concentration of 20.0 μg/mL rHuPH20 (at final concentration of 100 U/mL of Humulin-R).

Inclusion Criteria:

• Male or female of age 18 to 65 years, inclusive. Females of child-bearing potential must use a standard and effective means of birth control for the duration of the study.
• Participants with Type 1 diabetes mellitus treated with insulin for greater than or equal to 12 months.
• Body mass index (BMI) 18.0 to 29.0 kilograms per meter squared (kg/m^2), inclusive.
• Glycosylated hemoglobin A1c (HbA1c) less than or equal to 10% based on local laboratory results.
• Fasting C-peptide less than 0.6 nanograms per milliliter (ng/mL).
• Current treatment with insulin less than 1.2 units per kilogram per day (U/kg/day).
• Participants should be in good general health based on medical history and physical examination, without medical conditions that might prevent the completion of study drug injections and assessments required in this protocol.

Exclusion Criteria:

• Known or suspected allergy to any component of any of the study drugs in this trial.
• Previous enrollment in this trial.
• A participant who has proliferative retinopathy or maculopathy, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
• Clinically significant (as judged by the Investigator) active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram [ECG]), hepatic, neurological, renal, genitourinary, or hematological systems, or uncontrolled hypertension (diastolic blood pressure greater than or equal to 100 millimeters of mercury [mmHg] and/or systolic blood pressure greater than or equal to 160 mmHg after 5 minutes in the supine position).
• History of any illness or disease that in the opinion of the Investigator might confound the results of the trial or pose additional risk in administering the study drugs to the participant.
• Clinically significant findings (as judged by the Investigator) in routine laboratory data, including anemia with hemoglobin less than lower limits of normal at screening.
• Use of drugs which may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia.
• Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator.
• Current addiction to alcohol or substances of abuse as determined by the Investigator.
• Blood donation (>500 milliliters [mL]) within the 9 weeks prior to first day of dosing on study.
• Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device [IUD], oral or injectable contraceptives or barrier methods).
• Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation.
• Symptomatic gastroparesis.
• History or evidence of use of any tobacco- or nicotine-containing product within 6 months of screening or screening quantitative urine nicotine concentration >50 ng/mL.
• Receipt of any investigational drug within 4 weeks of first day of dosing in this study.
• Any condition (intrinsic or extrinsic) that in the judgment of the Investigator will interfere with trial participation or evaluation of data.

All participants who received at least 1 dose of Humalog, Humulin-R, or recombinant human hyaluronidase PH20 (rHuPH20).

Adverse event data collected from Day 1 through to the end of the study, for up to 80 days.