A Study in Healthy Subjects to Assess the Safety, Tolerability, PK and PD of HTL0030310

NCT03847207 | Completed Phase 1

• 3 other identifiers: HTL0030310-1012018-003169-33QSC200729
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1, first in human, three-part, single centre study to assess the safety, tolerability, PK and PD of single ascending subcutaneous doses of HTL0030310 in healthy subjects

Conditions

Healthy

Keywords

First in Human; Single Ascending Dose

Outcome Measures

Primary Outcomes (4)

• Part 1: Number of treatment related adverse events (as determined by abnormal clinical laboratory tests, vitals signs, ECG parameters, Holter ECG parameters and injection site reactions)

  Safety and Tolerability

  Admission up to 8 days post dose

• Part 2 and Part 3 Area under the effect time curve (EAUC) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol

  Pharmacodynamics

  Predose up to 4 hours post dose

• Part 2 and Part 3 Maximum observed effect (EMax) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol

  Pharmacodynamics

  Predose up to 4 hours post dose

• Part 2 and Part 3 Time to reach Maximum observed effect (TEMax) 1) for insulin, glucose, glucagon, GLP1, C-peptide and GIP level 2) for GH 3) ACTH and cortisol

  Pharmacodynamics

  Predose up to 4 hours post dose

Secondary Outcomes (10)

• Part 1 Maximum observed plasma concentration (Cmax) of single subcutaneous doses of HTL0030310

  Pre dose to 144 hours post dose

• Part 1 Time to reach Maximum observed plasma concentration (Tmax) of single subcutaneous doses of HTL0030310

  Pre dose to 144 hours post dose

• Part 1 Area under the curve (AUC) of single subcutaneous doses of HTL0030310

  Pre dose to 144 hours post dose

• Part 2 Maximum observed plasma concentration (Cmax) of single subcutaneous doses of pasireotide

  Predose to 24 hours postdose

• Part 2 Time to reach Maximum observed plasma concentration (Tmax) of single subcutaneous doses of pasireotide

  Predose to 24 hours postdose

Study Arms (3)

Part 1 Single Ascending Dose

EXPERIMENTAL

Eight subjects in up to 8 cohorts will be dosed. A single subcutaneous injection of HTL0030310 or placebo will be administered. In each cohort, 6 subjects will receive HTL0030310 and 2 subjects will receive placebo.

Drug: HTL0030310; Drug: Placebo

Part 2 Pasireotide PD Assessment

EXPERIMENTAL

Sixteen subjects in 2 cohorts (8 subjects per cohort) will be dosed on 4 occasions. Within each cohort, 4 subjects will be randomised to active dosing with CRH with desmopressin, GHRH and OGTT challenge and 4 subjects will be randomised to placebo dosing with CRH with desmopressin, GHRH and OGTT challenge.

Drug: Pasireotide; Drug: Placebo

Part 3 Proof of Pharmacological Effect

EXPERIMENTAL

Up to 80 subjects in 4 cohorts (up to 20 subjects per cohort) will be dosed in up to 3 study periods. In each period, subjects will receive active drug or placebo with GHRH, OGTT and CRH with desmopressin (optional).

Drug: HTL0030310; Drug: Placebo

Interventions

HTL0030310 DRUG

Solution for Subcutaneous injection

Part 1 Single Ascending Dose; Part 3 Proof of Pharmacological Effect

Pasireotide DRUG

Pasireotide 600 μg for subcutaneous injection

Part 2 Pasireotide PD Assessment

Placebo DRUG

Matching placebo Solution

Part 1 Single Ascending Dose; Part 2 Pasireotide PD Assessment; Part 3 Proof of Pharmacological Effect

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males or healthy a woman is considered of childbearing potentiaL (WONCBP); a WONCBP unless she is permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone \[FSH\] concentration ≥40 IU/L).
• Age 18 to 50 years of age
• A BMI of 20.0 to 30.0 kg/m2, with a minimum weight of 45 kg
• Must be willing and able to communicate and participate in the whole study
• Must provide written informed consent
• Must agree to adhere to the contraception requirements defined in the protocol (Section 9.4)

You may not qualify if:

• Subjects who have received any IMP in a clinical research study within the previous 3 months of screening
• Subjects who are study site employees, or immediate family members of a study site or sponsor employee
• Subjects who have previously been enrolled in this study. Subjects who have taken part in Part 1/Part 2 are not permitted to take part in Part 2/Part 3
• History of any drug or alcohol abuse in the past 2 years
• Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type)
• Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening and admission
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
• Females of childbearing potential. A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum FSH concentration ≥40 IU/L). All female subjects must have a negative urine pregnancy test
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
• Subjects with vital signs outside the normal range for healthy volunteers (HR \< 50 or \>90 bpm; Systolic BP \> 140 mmHg; Diastolic BP \> 90 mmHg)
• Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1 of the protocol)
• Fasting blood glucose at screening above the upper limit of normal (3.9 to 5.8 mM)
• HbA1c at screening above the upper limit of normal (\>6%)
• Abnormal renal function - defined as creatinine clearance \< 70mL/min using the Cockcroft-Gault equation at screening
• Abnormal hepatic function - defined as ALT, AST and total bilirubin \> 1.5 x upper limit of normal at screening

Sponsors & Collaborators

• Nxera Pharma UK Limited: lead

Study Sites (1)

Quotient Sciences

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

pasireotide

Study Officials

• Philip Evans, MBChB

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: February 20, 2019
• Study Start: January 23, 2019
• Primary Completion: March 5, 2020
• Study Completion: March 5, 2020
• Last Updated: February 19, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)