Phase 4
Completed N=16
A Phase IV, Open Label, 4-period Cross-over Study to Investigate a Drug Interaction Between Lamivudine and Sorbitol Oral Solutions in Healthy Volunteers
Infection, Human Immunodeficiency Virus
Source: ClinicalTrials.gov NCT02634073 ↗
Enrolled (actual)
16
Serious AEs
0.0%
Results posted
May 2017
Primary outcomePrimary: Plasma Lamivudine Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point (AUC[0-t]), AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) and AUC From Time Zero to 24 Hours (AUC[0-24]) — 13.2; 11.3; 8.93; 8.60 hour (h)*microgram (mcg)/milliliter (mL)
◆ Published Evidence
Established
35citations · ~4 / year
Effect of Sorbitol on the Pharmacokinetic Profile of Lamivudine Oral Solution in Adults: An Open-Label, Randomized Study.
Summary
Lamivudine (3TC) is a nucleoside analogue indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and children. Documented literature elucidates that simultaneous administration of multiple sorbitol-containing products could increase the potential for a significant interaction and may contribute to the lower 3TC exposures.
In this study several sorbitol doses (3.2 gram (g), 10.2 g, and 13.4 g solutions) will be administered with lamivudine to investigate dose dependency and mimic the situation where multiple sorbitol-containing antiretroviral medications may be co-administered with lamivudine. It will be open label, randomized, 4-way crossover (by William's design method) design at a single centre. Randomized participants will receive a single dose of each of four treatments after wash out period of minimum 7 days.
Linked Publications
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Effect of Sorbitol on the Pharmacokinetic Profile of Lamivudine Oral Solution in Adults: An Open-Label, Randomized Study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Plasma Lamivudine Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point (AUC[0-t]), AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) and AUC From Time Zero to 24 Hours (AUC[0-24]) |
13.2; 11.3; 8.93; 8.60; 12.4; 9.96 | — |
| PRIMARY Plasma Lamivudine Maximum Observed Concentration (Cmax), Concentration at 24 Hour (h) Post-dose (C24) and Last Measurable Concentration (Ct) |
0.036; 0.036; 0.041; 0.039; 0.013; 0.017 | — |
| PRIMARY Lamivudine Elimination Half-life in Plasma (t1/2) |
13.9; 19.0; 21.2; 17.3 | — |
| PRIMARY Plasma Lamivudine Apparent Oral Clearance (CL/F) |
22.738; 26.621; 33.608; 34.875 | — |
| PRIMARY Time to Observed Maximum Lamivudine Plasma Concentration (Tmax), Time of Last Measurable Plasma Concentration (Tlast) and Absorption Lag Time in Plasma (Tlag) |
0.75; 1.000; 1.00; 1.26; 48.00; 48.00 | — |
| SECONDARY Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAE) |
1; 2; 1; 1; 0; 0 | — |
| SECONDARY Change From Baseline in Pulse Rate |
6.5; 3.9; 6.0; 7.4; 5.8; 5.8 | — |
| SECONDARY Change From Baseline in Body Temperature |
0.03; 0.07; 0.08; -0.03; -0.01; -0.01 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
5.1; 4.5; 2.1; 5.6; 4.6; 4.6 | — |
| SECONDARY Number of Participants With Treatment Emergent Laboratory Abnormality Grade |
1; 1; 1; 1; 1; 1 | — |
| SECONDARY Change From Baseline in Erythrocytes |
0.351; 0.389; 0.339; 0.380; 0.142; 0.142 | — |
| SECONDARY Change From Baseline in Hematocrit |
0.0338; 0.0378; 0.0308; 0.0353; 0.0091; 0.0091 | — |
| SECONDARY Change From Baseline in Hemoglobin |
10.1; 10.9; 9.8; 9.9; 3.4; 3.4 | — |
| SECONDARY Change From Baseline in Mean Corpuscular Hemoglobin (MCH) |
0.02; -0.03; 0.06; -0.24; -0.14; -0.14 | — |
| SECONDARY Change From Baseline in Mean Corpuscular Volume (MCV) |
0.71; 0.63; 0.35; 0.44; -0.77; -0.77 | — |
| SECONDARY Change From Baseline in Platelets, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils |
19.2; 13.9; 13.8; 6.1; 2.3; 2.3 | — |
| SECONDARY Change From Baseline in Blood Urea Nitrogen (BUN), Sodium, Potassium, Glucose, Calcium |
-0.0892; -0.5578; 0.0223; 0.0446; -0.4909; -0.4909 | — |
| SECONDARY Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphates |
-3.1; -3.5; -2.3; -19.1; 1.1; 1.1 | — |
| SECONDARY Change From Baseline in Creatinine, Total Bilirubin and Direct Bilirubin |
3.86759; 2.21005; 4.42010; 0.55251; 0.00000; 0.00000 | — |
| SECONDARY Change From Baseline in Albumin |
1.8; 2.3; 2.1; 2.1; 0.6; 0.6 | — |
Eligibility Criteria
Inclusion Criteria
- Between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination and laboratory tests.
- A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body weight >=50 kilogram (kg) (110 pounds [lb]) for men and >45 kg (99 lb) for women and body mass index (BMI) within the range 18.5 - 31 kg/meter square (m^2) (inclusive).
- Male or Female. Females A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented Bilateral Oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.
Exclusion Criteria
- ALT and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 450 milli-seconds (msec).
Notes:
- The QTc is the QT interval corrected for heart rate according to Fridericia's formula, machine-read or manually over-read.
- The specific formula that will be used to determine eligibility and discontinuation for an individual participant should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual participant and then the lowest QTc value used to include or discontinue the participant from the trial.
- For purposes of data analysis, Corrected QT interval according to Bazett's formula (QTcB), QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the Reporting and Analysis Plan (RAP).
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise participant safety.
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 millilitre [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products
Data sourced from ClinicalTrials.gov (NCT02634073) and the linked publication. 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.